TNFR1 is essential for CD40, but not for lipopolysaccharide-induced sickness behavior and clock gene dysregulation

Autoimmune and infectious diseases are associated with behavioral changes referred to as sickness behavior syndrome (SBS). In autoimmunity, the generation of anti-self T lymphocytes and autoantibodies critically involves binding of CD40 ligand on T-cells to its receptor CD40 on B-cells, dendritic cells and macrophages. Activation of CD40 leads to production of proinflammatory cytokines and, as shown here, induces SBS. Here we report that these behavioral changes depend on the expression of tumor necrosis factor alpha receptor 1 (TNFR1), but not on interleukin-1 receptor 1 or interleukin-6. Moreover, the intensity of SBS correlates with suppression of E-box controlled clock genes, including Dbp, and upregulation of Bmal1. However, the absence of TNFR1 does not interfere with the development of SBS and dysregulation of clock genes in mice treated with lipopolysaccharide. Thus, our results suggest that TNFR1 mediates SBS and dysregulation of clock genes in autoimmune diseases.

Are there cervical spine findings at MR imaging that are specific to acute symptomatic whiplash injury? A prospective controlled study with four experienced blinded readers

To compare the magnetic resonance (MR) imaging findings in patients with acute whiplash injury with those in matched control subjects.

How valuable are multiple treatment comparison methods in evidence-based health-care evaluation?

Objectives To compare the use of pair-wise meta-analysis methods to multiple treatment comparison (MTC) methods for evidence-based health-care evaluation to estimate the effectiveness and cost-effectiveness of alternative health-care interventions based on the available evidence. Methods Pair-wise meta-analysis and more complex evidence syntheses, incorporating an MTC component, are applied to three examples: 1) clinical effectiveness of interventions for preventing strokes in people with atrial fibrillation; 2) clinical and cost-effectiveness of using drug-eluting stents in percutaneous coronary intervention in patients with coronary artery disease; and 3) clinical and cost-effectiveness of using neuraminidase inhibitors in the treatment of influenza. We compare the two synthesis approaches with respect to the assumptions made, empirical estimates produced, and conclusions drawn. Results The difference between point estimates of effectiveness produced by the pair-wise and MTC approaches was generally unpredictable—sometimes agreeing closely whereas in other instances differing considerably. In all three examples, the MTC approach allowed the inclusion of randomized controlled trial evidence ignored in the pair-wise meta-analysis approach. This generally increased the precision of the effectiveness estimates from the MTC model. Conclusions The MTC approach to synthesis allows the evidence base on clinical effectiveness to be treated as a coherent whole, include more data, and sometimes relax the assumptions made in the pair-wise approaches. However, MTC models are necessarily more complex than those developed for pair-wise meta-analysis and thus could be seen as less transparent. Therefore, it is important that model details and the assumptions made are carefully reported alongside the results.

Not in the Legends

In writing “Not in the Legends”, one of the images and concepts which constantly returned was that of pilgrimage. I began to write these poems while studying abroad in London, after having passed the previous semester in France and travelling around Europe. There was something in the repetition of sightseeing— walking six miles in Luxembourg to see the grave of General Patton, taking photographs of the apartment where Sylvia Plath ended her life, bowing before the bones of saints, searching through Père Lachaise for the grave of Théodore Gericault— which struck me as numinous and morbid. At the same time, I came to love living abroad and I grew discontent with both remaining and returning. I wanted the opportunity to live everywhere all the time and not have to choose between home and away. Returning from abroad, I turned my attention to the landscape of my native country. I found in the New England pilgrims a narrative of people who had left their home in search of growth and freedom. In these journeys I began to appreciate the significance of place and tried to understand what it meant to move from one place to another, how one chose a home, and why people searched for meaning in specific locations. The processes of moving from student to worker and from childhood to adulthood have weighed on me. I began to see these transitions towards maturity as travels to a different land. Memory and nostalgia are their own types of pilgrimage in their attempts to return to lost places, as is the reading of literature. These pilgrimages, real and metaphorical, form the thematic core of the collection. I read the work of many poets who came before me, returning to the places where the Canon was forged. Those poets have a large presence in the work I produced. I wondered how I, as a young poet, could earn my own place in the tradition and sought models in much the same way a painter studies the brushstrokes of a master. In the process, I have tried to uncover what it means to be a poet. Is it something like being a saint? Is it something like being a colonist? Or is to be the one who goes in search of saints and colonists? In trying to measure my own life and work based on the precedent, I have questioned what role era and generation have on the formation of identity. I focused my reading heavily on the early years of English poetry, trying to find the essence of the time when the language first achieved the transcendence of verse. In following the development of English poetry through Coleridge, John Berryman, and Allison Titus, I have explored the progression of those basic virtues in changing contexts. Those bearings, applied to my modern context, helped to shape the poetry I produced. Many of the poems in “Not in the Legends” are based on my own personal experience. In my recollections I have tried to interrogate nostalgia rather than falling into mere reminiscence. Rather than allowing myself poems of love and longing, I have tried to find the meaning of those emotions. A dominant conflict exists between adventure and comfort which mirrors the central engagement with the nature of being “here” or “there”. It is found in scenes of domesticity and wilderness as I attempt to understand my own simultaneous desire for both. For example, in “Canned Mangoes…” the intrusion of nature, even in a context as innocuous as a poem by Sir Walter Raleigh, unravels ordinary comforts of the domestic sphere. The character of “The Boy” from Samuel Beckett’s Waiting for Godot proved such an interesting subject for me because he is one who can transcend the normal boundaries of time and place. The title suggests connections to both place and time. “Legends” features the dual meaning of both myths and the keys to maps. To propose something “Not in the Legends” is to find something which has no precedent in our histories and our geographies, something beyond our field of knowledge and wholly new. One possible interpretation I devised was that each new generation lives a novel existence, the future being the true locus of that which is beyond our understanding. The title comes from Keats’ “Hyperion, a Fragment”, and details the aftermath of the Titanomachy. The Titans, having fallen to the Olympians, are a representation of the passing of one generation for the next. Their dejection is expressed by Saturn, who laments: Not in my own sad breast, Which is its own great judge and searcher out, Can I find reason why ye should be thus: Not in the legends of the first of days… (129-132) The emotions of the conquered Titans are unique and without antecedent. They are experiencing feelings which surpass all others in history. In this, they are the equivalent of the poet who feels that his or her own sufferings are special. In contrast are Whitman’s lines from “Song of Myself” which serve as an epigraph to this collection. He contends for a sense of continuity across time, a realization that youth, age, pleasure, and suffering have always existed and will always exist. Whitman finds consolation in this unity, accepting that kinship with past generations is more important that his own individuality. These opposing views offer two methods of presenting the self in history. The instinct of poetry suggests election. The poet writes because he feels his experiences are special, or because he believes he can serve as a synecdoche for everyone. I have fought this instinct by trying to contextualize myself in history. These poems serve as an attempt at prosopography with my own narrative a piece of the whole. Because the earth abides forever, our new stories get printed over the locations of the old and every place becomes a palimpsest of lives and acts. In this collection I have tried to untangle some of those layers, especially my own, to better understand the sprawling legend of history.

Species-Specific Relationships between Water Transparency and Male Coloration within and between Two Closely Related Lake Victoria Cichlid Species

Environmental variation in signalling conditions affects animal communication traits, with possible consequences for sexual selection and reproductive isolation. Using spectrophotometry, we studied how male coloration within and between populations of two closely related Lake Victoria cichlid species (Pundamilia pundamilia and P. nyererei) covaries with water transparency. Focusing on coloration patches implicated in sexual selection, we predicted that in clear waters, with broad-spectrum light, (1) colours should become more saturated and (2) shift in hue away from the dominant ambient wavelengths, compared to more turbid waters. We found support for these predictions for the red and yellow coloration of P. nyererei but not the blue coloration of P. pundamilia. This may be explained by the species difference in depth distribution, which generates a steeper gradient in visual conditions for P. nyererei compared to P. pundamilia. Alternatively, the importance of male coloration in intraspecific sexual selection may differ between the species. We also found that anal fin spots, that is, the orange spots on male haplochromine anal fins that presumably mimic eggs, covaried with water transparency in a similar way for both species. This is in contrast to the other body regions studied and suggests that, while indeed functioning as signals, these spots may not play a role in species differentiation.

Anti-oxidized low-density lipoprotein (oxLDL) antibody levels are not related to increasing circulating oxLDL concentrations during the course of pregnancy

To address the question of whether the high levels of oxidative modified low-density lipoproteins (oxLDL) in pregnancy are opposed by an appropriate humoral autoimmune response providing anti-oxLDL autoantibodies in maternal serum of healthy women throughout gestation.

Expansion on specific substrates regulates the phenotype and differentiation capacity of human articular chondrocytes

In this study, we investigated if monolayer expansion of adult human articular chondrocytes (AHAC) on specific substrates regulates cell phenotype and post-expansion multilineage differentiation ability. AHAC isolated from cartilage biopsies of five donors were expanded on plastic dishes (PL), on dishes coated with collagen type II (COL), or on slides coated with a ceramic material (Osteologic, OS). The phenotype of expanded chondrocytes was assessed by flow cytometry and real-time RT-PCR. Cells were then cultured in previously established conditions promoting differentiation toward the chondrogenic or osteogenic lineage. AHAC differentiation was assessed histologically, biochemically, and by real-time RT-PCR. As compared to PL-expanded AHAC, those expanded on COL did not exhibit major phenotypic changes, whereas OS-expanded cells expressed (i) higher bone sialoprotein (BSP) (22.6-fold) and lower collagen type II (9.3-fold) mRNA levels, and (ii) lower CD26, CD90 and CD140 surface protein levels (1.4-11.1-fold). Following chondrogenic differentiation, COL-expanded AHAC expressed higher mRNA levels of collagen type II (2.3-fold) and formed tissues with higher glycosaminoglycan (GAG) contents (1.7-fold), whereas OS-expanded cells expressed 16.5-fold lower collagen type II and generated pellets with 2.0-fold lower GAG contents. Following osteogenic differentiation, OS-expanded cells expressed higher levels of BSP (3.9-fold) and collagen type I (2.8-fold) mRNA. In summary, AHAC expansion on COL or OS modulated the de-differentiated cell phenotype and improved the cell differentiation capacity respectively toward the chondrogenic or osteogenic lineage. Phenotypic changes induced by AHAC expansion on specific substrates may mimic pathophysiological events occurring at different stages of osteoarthritis and may be relevant for the engineering of osteochondral tissues.

Predictors of oral health quality of life in older adults

There is limited information regarding oral health status and other predictors of oral health-related quality of life. An association between oral health status and perceived oral health-related quality of life (OHQOL) might help clinicians motivate patients to prevent oral diseases and improve the outcome of some dental public health programs. This study evaluated the relationship between older persons' OHQOL and their functional dentition, caries, periodontal status, chronic diseases, and some demographic characteristics. A group of 733 low-income elders (mean age 72.7 [SD = 4.71, 55.6% women, 55.1% members of ethnic minority groups in the U.S. and Canada) enrolled in the TEETH clinical trial were interviewed and examined as part of their fifth annual visit for the trial. OHQOL was measured by the Geriatric Oral Health Assessment Index (GOHAI); oral health and occlusal status by clinical exams and the Eichner Index; and demographics via interviews. Elders who completed the four-year assessment had an average of 21.5 teeth (SD = 6.9), with 8.5 occluding pairs (SD = 4.6), and 32% with occlusal contacts in all four occluding zones. Stepwise multiple regressions were conducted to predict total GOHAI and its subscores (Physical, Social, and Worry). Functional dentition was a less significant predictor than ethnicity and being foreign-born. These variables, together with gender, years since immigrating, number of carious roots, and periodontal status, could predict 32% of the variance in total GOHAI, 24% in Physical, 27% in Social, and 21% in the Worry subscales. These findings suggest that functional dentition and caries influence older adults' OHQOL, but that ethnicity and immigrant status play a larger role.

[Rumenocentesis: a suitable technique for analysis of rumen juice pH in cattle?]

In the United States, rumenocentesis has been recommended especially for early diagnosis of subacute rumen acidosis (SARA). The objective of the current study was to evaluate health risks due to the technique ofrumenocentesis and to measure pH in ruminal juice using a commercial indicator paper (Pehanon) and a pH electrode (reference method). After 11 dairy cows underwent rumenocentesis, the clinical status of those animals was evaluated daily, and cows were slaughtered as well as pathologically--anatomically examined on day 7. During the observation period, the following pathological clinical signs were evident: forced inspiration (3 cows), transient episode of hyperthermia (2 cows), increased tension of the abdominal wall (8 cows) and positive foreign body tests (3 cows). One cow had to be culled on day 7 because of severe generalised septic peritonitis spreading from the site of rumenocentesis. At slaughter, hematoma formation in the area of the puncture site was found in 9 out of 10 cows. It was concluded that the severe complications encountered with this technique do not legitimate rumenocentesis as a routine procedure for collection of rumen juice samples in cows under Swiss conditions. The correlation between the pH reference method and the commercial indicator paper was the high (r = 0.926).

Psychobiological responses to drug cues before and after methadone intake in heroin-dependent patients: A pilot study

Craving and stress frequently drive compulsive heroin use. Although methadone attenuates craving, drug-conditioned stimuli can trigger craving and possibly stress arousal in heroin-dependent patients receiving methadone maintenance. This study investigated drug cue-related craving, affectivity, and cortisol reactivity in 16 methadone-maintained patients before and after daily methadone. Unexpectedly, drug cues significantly increased craving after (t[15]=-4.27, p=0.001), but not before methadone intake. Patients displayed blunted cortisol response after post-methadone drug cues (t[15]=3.05, p=0.008) suggesting dissociated craving and cortisol reactivity after methadone intake of possible clinical relevance.