If it looks like a duck: Fish fit the criteria for pain perception

Whereas we have denied the experience of pain to animals, including human babies, the evidence is becoming clearer that animals across a variety of species have the capacity to feel pain (Bellieni, 2012). As converging findings are collected from pain studies and the study of cognition, it is becoming harder to deny that fish are among the species that do feel pain

If it looks like a duck: Fish fit the criteria for pain perception

Whereas we have denied the experience of pain to animals, including human babies, the evidence is becoming clearer that animals across a variety of species have the capacity to feel pain (Bellieni, 2012). As converging findings are collected from pain studies and the study of cognition, it is becoming harder to deny that fish are among the species that do feel pain

TNF and PGE2 in human monocyte-derived macrophages infected with Chlamydia trachomatis

In this study levels of prostaglandin E2 (PGE2), tumour necrosis factor (TNF) and interleukin-1 (IL-1) alpha in medium from monocyte derived macrophages (MdM) infected with Chlamydia trachomatis (L2/434/Bu or K biovars). TNF and PGE2 were found in both cases while IL-1 alpha was not detected. Both TNF and PGE2 levels were higher in the medium of the MdM infected with K biovars. TNF reached maximum levels 24 h postinfection, and then declined, while PGE2 levels increased continuously during the infection time up to 96 h post-infection. Addition of dexamethasone inhibited production of TNF and PGE2. Inhibition of PGE2 production by indomethacin resulted in increased production of TNF, while addition of PGE2 caused partial inhibition of TNF production from infected MdM

Socioeconomic Inequalities in Mortality Rates in Old Age in the World Health Organization Europe Region

Socioeconomic adversity is among the foremost fundamental causes of human suffering, and this is no less true in old age. Recent reports on socioeconomic inequalities in mortality rate in old age suggest that a low socioeconomic position continues to increase the risk of death even among the oldest old. We aimed to examine the evidence for socioeconomic mortality rate inequalities in old age, including information about associations with various indicators of socioeconomic position and for various geographic locations within the World Health Organization Region for Europe. The articles included in this review leave no doubt that inequalities in mortality rate by socioeconomic position persist into the oldest ages for both men and women in all countries for which information is available, although the relative risk measures observed were rarely higher than 2.00. Still, the available evidence base is heavily biased geographically, inasmuch as it is based largely on national studies from Nordic and Western European countries and local studies from urban areas in Southern Europe. This bias will hamper the design of European-wide policies to reduce inequalities in mortality rate. We call for a continuous update of the empiric evidence on socioeconomic inequalities in mortality rate

Wave-number locking in spatially forced pattern-forming systems

Abstract -We use the Swift-Hohenberg model and normal-form equations to study wave-number locking in two-dimensional systems as a result of one-dimensional spatially periodic weak forcing. The freedom of the system to respond in a direction transverse to the forcing leads to wavenumber locking in a wide range of forcing wave-numbers, even for weak forcing, unlike the locking in a set of narrow Arnold tongues in one-dimensional systems. Multi-stability ranges of stripe, rectangular, and oblique patterns produce a variety of resonant patterns. The results shed new light on rehabilitation practices of banded vegetation in drylands. Copyright c EPLA, 2008 Frequency locking phenomena in temporally forced oscillators are well understood; a forced oscillator can adjust its frequency of oscillation to a rational fraction of the forcing frequency The spatial counterpart of frequency locking, wavenumber locking, is less well understood. Although much work has been devoted to pattern-forming systems that are subjected to spatially periodic forcing In this letter we analyze wave-number locking phenomena associated with a two-dimensional response to a one-dimensional forcing. We are interested in universal aspects of wave-number locking and therefore base our study on normal-form equations. We derive these equations using a periodically forced Swift-Hohenberg (SH) equation, which helps us motivate the problem and test our analysis using direct numerical solutions. The specific equation we consider is In this equation ε is the distance from the instability point of the unforced zero state to a stationary pattern with a wave-number k 0 ∼ O(1), k f is the forcing wave-number, γ is the intensity of multiplicative forcing and α is the intensity of additive forcing. In the absence of forcing (α = γ = 0) the unstable zero state u = 0 evolves towards a stripe pattern with wavenumber k 0 , the pattern that minimizes the Lyapunov function of the SH equation (se

Patterns, Predictors, and Outcomes of Falls Trajectories in Older Adults: The MOBILIZE Boston Study with 5 Years of Follow-Up

Background: Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified. Methods: We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories. Results: We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50–2.56)) and fall in the past year (OR 3.52 (95CI, 2.16–6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4–13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34–5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60–3.16)) and fall in the past year (OR 3.82 (95CI, 2.34–6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63–169) per 1,000 person-years; Injurious falls 172 (95% CI 111–237) per 1,000 person-years and Fractures 41 (95% CI 9–78) per 1,000 person-years. Conclusions: Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures

The unfolded protein response affects readthrough of premature termination codons

One-third of monogenic inherited diseases result from premature termination codons (PTCs). Readthrough of in-frame PTCs enables synthesis of full-length functional proteins. However, extended variability in the response to readthrough treatment is found among patients, which correlates with the level of nonsense transcripts. Here, we aimed to reveal cellular pathways affecting this inter-patient variability. We show that activation of the unfolded protein response (UPR) governs the response to readthrough treatment by regulating the levels of transcripts carrying PTCs. Quantitative proteomic analyses showed substantial differences in UPR activation between patients carrying PTCs, correlating with their response. We further found a significant inverse correlation between the UPR and nonsense-mediated mRNA decay (NMD), suggesting a feedback loop between these homeostatic pathways. We uncovered and characterized the mechanism underlying this NMD-UPR feedback loop, which augments both UPR activation and NMD attenuation. Importantly, this feedback loop enhances the response to readthrough treatment, highlighting its clinical importance. Altogether, our study demonstrates the importance of the UPR and its regulatory network for genetic diseases caused by PTCs and for cell homeostasis under normal conditions

Protandric Transcriptomes to Uncover Parts of the Crustacean Sex-Differentiation Puzzle

Hermaphrodite systems offer unique opportunities to study sexual differentiation, due to their high degree of sexual plasticity and to the fact that, unlike gonochoristic systems, the process is not confined to an early developmental stage. In protandric shrimp species, such as Hippolyte inermis and Pandalus platyceros, male differentiation is followed by transformation to femaleness during adulthood. The mechanisms controlling sexual differentiation have not been fully elucidated in crustaceans, but a key role has been attributed to the insulin-like hormone (IAG) produced by the androgenic gland (AG), a crustacean masculine endocrine organ. To uncover further transcriptomic toolkit elements affecting the sexual differentiation of H. inermis, we constructed eye and whole body RNA libraries of four representative stages during its protandric life cycle (immature, male, young female and mature female). The body libraries contained transcripts related to the reproductive system, among others, while the eye libraries contained transcripts related to the X-organ-sinus gland, a central endocrine complex that regulates crustacean reproduction. Binary pattern analysis, performed to mine for genes expressed differentially between the different life stages, yielded 19,605 and 6,175 transcripts with a specific expression pattern in the eye and body, respectively. Prominent sexually biased transcriptomic patterns were recorded for the IAG and vitellogenin genes, representing, respectively, a key factor within the masculine IAG-switch, and a precursor of the yolk protein, typical of feminine reproductive states. These patterns enabled the discovery of novel putative protein-coding transcripts exhibiting sexually biased expression in the H. inermis body and eye transcriptomes of males and females. Homologs to the above novel genes have been found in other decapod crustaceans, and a comparative study, using previously constructed transcriptomic libraries of another protandric shrimp, P. platyceros, showed similar sexually biased results, supporting the notion that such genes, mined from the H. inermis transcriptome, may be universal factors related to reproduction and sexual differentiation and their control in other crustaceans. This study thus demonstrates the potential of transcriptomic studies in protandric species to uncover unexplored layers of the complex crustacean sex-differentiation puzzle

Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial

Spinocerebellar ataxia (SCA) is a neurodegenerative disorder caused by dysfunction of the cerebellum and its connected neural networks. There is currently no cure for SCA and symptomatic treatment remains limited. We aimed here to examine the effects of a repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum on clinical impression, postural control and gait in patients with SCA. In this randomized, double-blinded and sham-controlled study, 20 individuals aged 18–75 years with SCA confirmed by genetic testing completed rTMS or sham intervention comprising 20 sessions of MRI-guided stimulation over the cerebellum. Baseline assessments included the Standard Ataxia Rating Assessment (SARA), the 9-hole peg test of manual dexterity, the Timed Up-and-Go (TUG) test, standing postural control with eyes-open and eyes-closed, and gait. Immediate (within 1-week) and 1-month follow-ups were completed. Intervention compliance was high (19 ± 2 of 20 sessions) and no rTMS-related adverse events were reported. rTMS, compared to sham, was associated with greater percent improvement in SARA total score from baseline to the 1-month follow-up (p = 0.008). Secondary analyses of individual SARA items revealed that rTMS improved performance within the “stance” sub-score only (p = 0.002). This functional change was accompanied by improvement to several objective metrics of postural sway during eyes-open and eyes-closed standing (p < 0.008). rTMS did not influence the 9-hole peg test, TUG, or gait kinematics. A 20-session rTMS intervention is safe and feasible for those with SCA. Additional research is warranted to confirm the observed longer-term benefits of this intervention on standing postural control.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT0197590