Pharmacotherapy during pregnancy, childbirth and lactation: points and principles to consider (a 2015 update)

Pregnancy, childbirth and lactation pose unique challenges in terms of drug therapy. The pregnant mother and her unborn child are exceptionally vulnerable from a physiological, clinical and ethical standpoint. This warrants careful consideration with respect to a number of important aspects, which could firstly influence the decision to opt for drug therapy, and secondly, could influence the specific agent selected for each indication. The US Food and Drug Administration has introduced changes to the content and format of information presented in prescription drug labelling to assist healthcare providers when assessing benefit versus risk, and in the subsequent counselling of pregnant woman and nursing mothers who need to take medication. This change came into effect at the end of June 2015. This article provides an overview of these important aspects.Keywords: embryo, foetus, lactation, neonate, pregnanc

Immunology for Clinicians: A ‘Trojan Horse’ approach

A South African website imparts basic immunology information to clinicians and other health care workers

Non-IgE-mediated food allergies

Non-imunoglobulin E (IgE)-mediated conditions include combined IgE and cell-mediated conditions such as atopic dermatitis and eosinophilic oesophagitis, and pure T-cell-mediated conditions such as food protein-induced enterocolitis syndrome, allergic proctocolitis and enteropathy syndromes. Diagnosing mixed or non-IgE-mediated allergy is challenging. A clear cause-effect relationship between exposure to the suspected food and symptoms is not always possible, as symptoms develop over time and are more chronic in nature. Skin-prick tests and specific IgE to the allergen are usually negative. An elimination diet may be necessary to diagnose non-IgE-mediated type food allergy. The suspected allergen should be excluded from the diet for 2 - 6 weeks under dietetic guidance to assess for improvement of symptoms. After symptom improvement, a rechallenge is necessary to definitively prove causal relation.

Transport processes investigation: A necessary first step in site scale characterization plans

We propose an approach, which we call the Transport Processes Investigation or TPI, to identify and verify site-scale transport processes and their controls. The TPI aids in the formulation of an accurate conceptual model of flow and transport, an essential first step in the development of a cost effective site characterization strategy. The TPI is demonstrated in the highly complex vadose zone of glacial tills that underlie the Fernald Environmental Remediation Project (FEMP) in Fernald, Ohio. As a result of the TPI, we identify and verify the pertinent flow processes and their controls, such as extensive macropore and fracture flow through layered clays, which must be included in an accurate conceptual model of site-scale contaminant transport. We are able to conclude that the classical modeling and sampling methods employed in some site characterization programs will be insufficient to characterize contaminant concentrations or distributions at contaminated or hazardous waste facilities sited in such media

Identifying nucleic acid-associated proteins in Mycobacterium smegmatis by mass spectrometry-based proteomics

Abstract Background Transcriptional responses required to maintain cellular homeostasis or to adapt to environmental stress, is in part mediated by several nucleic-acid associated proteins. In this study, we sought to establish an affinity purification-mass spectrometry (AP-MS) approach that would enable the collective identification of nucleic acid-associated proteins in mycobacteria. We hypothesized that targeting the RNA polymerase complex through affinity purification would allow for the identification of RNA- and DNA-associated proteins that not only maintain the bacterial chromosome but also enable transcription and translation. Results AP-MS analysis of the RNA polymerase β-subunit cross-linked to nucleic acids identified 275 putative nucleic acid-associated proteins in the model organism Mycobacterium smegmatis under standard culturing conditions. The AP-MS approach successfully identified proteins that are known to make up the RNA polymerase complex, as well as several other known RNA polymerase complex-associated proteins such as a DNA polymerase, sigma factors, transcriptional regulators, and helicases. Gene ontology enrichment analysis of the identified proteins revealed that this approach selected for proteins with GO terms associated with nucleic acids and cellular metabolism. Importantly, we identified several proteins of unknown function not previously known to be associated with nucleic acids. Validation of several candidate nucleic acid-associated proteins demonstrated for the first time DNA association of ectopically expressed MSMEG_1060, MSMEG_2695 and MSMEG_4306 through affinity purification. Conclusions Effective identification of nucleic acid-associated proteins, which make up the RNA polymerase complex as well as other DNA- and RNA-associated proteins, was facilitated by affinity purification of the RNA polymerase β-subunit in M. smegmatis. The successful identification of several transcriptional regulators suggest that our approach could be sensitive enough to investigate the nucleic acid-associated proteins that maintain cellular functions and mediate transcriptional and translational change in response to environmental stress

Strong-coupling expansion and effective hamiltonians

When looking for analytical approaches to treat frustrated quantum magnets, it is often very useful to start from a limit where the ground state is highly degenerate. This chapter discusses several ways of deriving {effective Hamiltonians} around such limits, starting from standard {degenerate perturbation theory} and proceeding to modern approaches more appropriate for the derivation of high-order effective Hamiltonians, such as the perturbative continuous unitary transformations or contractor renormalization. In the course of this exposition, a number of examples taken from the recent literature are discussed, including frustrated ladders and other dimer-based Heisenberg models in a field, as well as the mapping between frustrated Ising models in a transverse field and quantum dimer models.Comment: To appear as a chapter in "Highly Frustrated Magnetism", Eds. C. Lacroix, P. Mendels, F. Mil

Symposium for Miroslav Hroch

Twelve historians and social scientists reflect on Miroslav Hroch's contributions to the field of nationalism studies. There are essays on his pioneering comparative historical studies of ‘small nation’ national movements and his distinction between nationalism and national movements. Other essays focus on concepts such as those of protagonist, the three phases of national movements, the small nation and nationally relevant conflict of interest. A further set of essays explores how Hroch's approach can be extended beyond small nations, beyond Europe and into the contemporary period.Political Culture and National Identit

The association between contrast-enhanced ultrasound and near-infrared spectroscopy-derived measures of calf muscle microvascular responsiveness in older adults

Background and Aim Contrast-enhanced ultrasound (CEUS) measures of post-occlusion skeletal muscle microvascular responsiveness demonstrate the microvascular dysfunction associated with ageing and age-related disease. However, the accessibility of CEUS is limited by the need for intravenous administration of ultrasound contrast agents and sophisticated imaging analysis. Alternative methods are required for the broader assessment of microvascular dysfunction in research and clinical settings. Therefore, we aimed to evaluate the level of association and agreement between CEUS and near-infrared spectroscopy (NIRS)-derived measures of post-occlusion skeletal muscle microvascular responsiveness in older adults. Methods During supine rest, participants (n=15, 67±11 years) underwent 5 minutes of thigh cuff-occlusion (200 mmHg). Post-occlusion CEUS measures of calf muscle microvascular responsiveness were made, including time to 95% peak acoustic intensity (TTP95 AI) and the rate of rise (slope AI). Simultaneous measures, including time to 95% peak oxygenated haemoglobin (TTP95 O2Hb) and slope O2Hb, were made using continuous-wave NIRS in the same muscle region. Results There were strong correlations between TTP95 measures derived from CEUS and NIRS (r=0.834, p=<0.001) and the corresponding measures of slope (r=0.735, p=0.004). The limits of agreement demonstrated by Bland Altman plot analyses for CEUS and NIRS-derived measures of TTP95 (-9.67–1.98 s) and slope (-1.29–5.23%. s-1) were smaller than the minimum differences expected in people with microvascular dysfunction. Conclusions The strong correlations and level of agreement in the present study support the use of NIRS as a non-invasive, portable and cost-effective method for assessing post-occlusion skeletal muscle microvascular responsiveness in older adults