Severity of Giardia infection associated with post-infectious fatigue and abdominal symptoms two years after

<p>Abstract</p> <p>Background</p> <p>A high rate of post-infectious fatigue and abdominal symptoms two years after a waterborne outbreak of giardiasis in Bergen, Norway in 2004 has previously been reported. The aim of this report was to identify risk factors associated with such manifestations.</p> <p>Methods</p> <p>All laboratory confirmed cases of giardiasis (n = 1262) during the outbreak in Bergen in 2004 received a postal questionnaire two years after. Degree of post-infectious abdominal symptoms and fatigue, as well as previous abdominal problems, was recorded. In the statistical analyses number of treatment courses, treatment refractory infection, delayed education and sick leave were used as indices of protracted and severe <it>Giardia </it>infection. Age, gender, previous abdominal problems and symptoms during infection were also analysed as possible risk factors. Simple and multiple ordinal logistic regression models were used for the analyses.</p> <p>Results</p> <p>The response rate was 81% (1017/1262), 64% were women and median age was 31 years (range 3-93), compared to 61% women and 30 years (range 2-93) among all 1262 cases. Factors in multiple regression analysis significantly associated with abdominal symptoms two years after infection were: More than one treatment course, treatment refractory infection, delayed education, bloating and female gender. Abdominal problems prior to <it>Giardia </it>infection were not associated with post-infectious abdominal symptoms. More than one treatment course, delayed education, sick leave more than 2 weeks, and malaise at the time of infection, were significantly associated with fatigue in the multiple regression analysis, as were increasing age and previous abdominal problems.</p> <p>Conclusion</p> <p>Protracted and severe <it>giardiasis </it>seemed to be a risk factor for post-infectious fatigue and abdominal symptoms two years after clearing the <it>Giardia </it>infection.</p

Learning environment associated with use of mixed mode delivery model among secondary business studies students in Singapore

At many teacher education institutes around the world, preservice teachers are empowered to use pedagogical tools and strategies that engage their students. We used a modified version of the Constructivist Learning Environment Survey (CLES) to evaluate the effectiveness of a pedagogical model known as the Mixed Mode Delivery (MMD) model in terms of the CLES’s five scales of personal relevance, uncertainty, critical voice, shared control and negotiation. Comparisons were made between 2,216 secondary school students taught by the preservice teachers in an MMD group and 991 students in a control group in terms of the relative magnitudes of the gap between the actual and preferred learning environment in students’ school classrooms. The findings supported the positive impact of using MMD in terms of students’ perceptions of their classroom environments for all CLES scales

Multiple Chronic Conditions: Prevalence, Health Consequences, and Implications for Quality, Care Management, and Costs

Persons with multiple chronic conditions are a large and growing segment of the US population. However, little is known about how chronic conditions cluster, and the ramifications of having specific combinations of chronic conditions. Clinical guidelines and disease management programs focus on single conditions, and clinical research often excludes persons with multiple chronic conditions. Understanding how conditions in combination impact the burden of disease and the costs and quality of care received is critical to improving care for the 1 in 5 Americans with multiple chronic conditions. This Medline review of publications examining somatic chronic conditions co-occurring with 1 or more additional specific chronic illness between January 2000 and March 2007 summarizes the state of our understanding of the prevalence and health challenges of multiple chronic conditions and the implications for quality, care management, and costs

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

BACKGROUND:Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. METHODOLOGY/PRINCIPAL FINDINGS:We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T-->S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. CONCLUSIONS/SIGNIFICANCE:The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features

The Interplay of Variants Near LEKR and CCNL1 and Social Stress in Relation to Birth Size

Background We previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. Here, we study the impact of these variants and social stress during pregnancy, defined as social adversity and neighborhood disparity, on infant birth size. We aimed to determine whether the addition of genetic variance magnified the observed associations. Methodology/Principal Findings We analyzed data from the Northern Finland Birth Cohort 1986 (n = 5369). Social adversity was defined by young maternal age (<20 years), low maternal education (<11 years), and/or single marital status. Neighborhood social disparity was assessed by discrepancy between neighborhoods relative to personal socio-economic status. These variables are indicative of social and socioeconomic stress, but also of biological risk. The adjusted multiple regression analysis showed smaller birth size in both infants of mothers who experienced social adversity (birthweight by −40.4 g, 95%CI −61.4, −19.5; birth length −0.14 cm, 95%CI −0.23, −0.05; head circumference −0.09 cm 95%CI −0.15, −0.02) and neighborhood disparity (birthweight −28.8 g, 95%CI −47.7, −10.0; birth length −0.12 cm, 95%CI −0.20, −0.05). The birthweight-lowering risk allele (SNP rs900400 near LEKR and CCNL1) magnified this association in an additive manner. However, likely due to sample size restriction, this association was not significant for the SNP rs9883204 in ADCY5. Birth size difference due to social stress was greater in the presence of birthweight-lowering alleles. Conclusions/Significance Social adversity, neighborhood disparity, and genetic variants have independent associations with infant birth size in the mutually adjusted analyses. If the newborn carried a risk allele rs900400 near LEKR/CCNL1, the impact of stress on birth size was stronger. These observations give support to the hypothesis that individuals with genetic or other biological risk are more vulnerable to environmental influences. Our study indicates the need for further research to understand the mechanisms by which genes impact individual vulnerability to environmental insults

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Carrion Availability in Space and Time

Introduction Availability of carrion to scavengers is a central issue in carrion ecology and management, and is crucial for understanding the evolution of scavenging behaviour. Compared to live animals, their carcasses are relatively unpredictable in space and time in natural conditions, with a few exceptions (see below, especially Sect. “Carrion Exchange at the Terrestrial-Aquatic Interface”). Carrion is also an ephemeral food resource due to the action of a plethora of consumers, from microorganisms to large vertebrates, as well as to desiccation (i.e., loss of water content; DeVault et al. 2003; Beasley et al. 2012; Barton et al. 2013; Moleón et al. 2014). With a focus on vertebrate carcasses, here we give an overview of (a) the causes that produce carrion, (b) the rate of carrion production, (c) the factors affecting carrion quality, and (d) the distribution of carrion in space and time, both in terrestrial and aquatic environments (including their interface). In this chapter, we will focus on naturally produced carrion, whereas non-natural causes of animal mortality are described in chapter “Human-Mediated Carrion: Effects on Ecological Processes”. However, throughout this chapter we also refer to extensive livestock carrion, because in the absence of strong restrictions such as those imposed in the European Community after the bovine spongiform encephalopathy crisis (Donázar et al. 2009; Margalida et al. 2010), the spatiotemporal availability of carrion of extensive livestock and wild ungulates is similar

Azimuthal Charged-Particle Correlations and Possible Local Strong Parity Violation

Parity-odd domains, corresponding to nontrivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the system’s orbital momentum axis. We investigate a three-particle azimuthal correlator which is a P even observable, but directly sensitive to the charge separation effect. We report measurements of charged hadrons near center-of-mass rapidity with this observable in Au+Au and Cu+Cu collisions at √sNN=200  GeV using the STAR detector. A signal consistent with several expectations from the theory is detected. We discuss possible contributions from other effects that are not related to parity violation