Miracle-dz/UniFAR-FTUs huggingface dataset:
Pain assessment in intellectually disabled people: non-verbal indicators.

BACKGROUND Although important progress has been made during the past decade, research on pain in people with intellectual disabilities is still scarce. Pain assessment in people with intellectual disabilities is a frequent and difficult problem, especially for nurses working with people with intellectual disabilities on a daily basis. Gathering more information about pain in people with intellectual disabilities is of major importance and relevance for nursing, and adds to the developing body of knowledge. OBJECTIVE To investigate the nature and relative importance of non-verbal indicators used by nurses to assess pain in people with a severe or profound intellectual disability. METHODS A questionnaire consisting of 158 indicators of pain was used. A total of 135 nurses from nine institutions specializing in the care of people with intellectual disability were asked to rate each indicator on a scale of 1-10 to show which non-verbal expressions they considered important in diagnosing pain. RESULTS A total of 109 nurses responded. All 158 indicators were mentioned as being important to indicate pain. All except four had a range of 9. Seven (moaning during manipulation, crying during manipulation, painful facial expression during manipulation, swelling, screaming during manipulation, not using (affected) body part, and moving the body in a specific way of behaving) were reported as 'very important' by more than 50% of nurses. The lowest score (median 5.5; minimum 1, maximum 10) was given to the indicator 'waving arm movements'. The pain of people with severe intellectual disability appeared to be assessed differently from that of people with profound intellectual disability. Indicators belonging to the 'physiological' category scored relatively higher in the group of nurses specializing in profound disability. In contrast, indicators belonging to the 'social-emotional' category were scored relatively higher by nurses specializing in severe disability. CONCLUSION Nurses used a wide range of indicators to assess pain in people with intellectual disability. Functional abilities and level of disability seem to influence the indicators used.
Elevated Serum Levels of Calprotectin (Myeloid-Related Protein 8/14) in Patients With Ankylosing Spondylitis and Its Association With Disease Activity and Quality of Life

Background Calprotectin is one of the major leukocyte S100 proteins showing both calcium binding and antimicrobial characteristics. The serum level of calprotectin is markedly elevated in patients with inflammatory bowel disease, rheumatoid arthritis, as well as systemic lupus erythematosus and has been suggested to play a prominent role in both progression and pathogenesis of these diseases. Aim The purpose of this study was to investigate the serum level of calprotectin in patients with ankylosing spondylitis (AS) and its association with disease activity and other clinical characteristics of AS. Materials and Methods Thirty-one patients who met the modified New York criteria for AS and 45 healthy controls were included in this study. Both Bath AS disease activity index and AS disease activity score were applied on the patients with AS for the assessment of disease activity; Bath AS functional index, for the assessment of functional activity; Bath AS radiology index, for the assessment of radiological damage; and the AS quality of life questionnaire for the assessment of disease-related life status. Spinal and hip measurements were performed using Bath AS metrology index. The serum level of calprotectin was determined using enzyme-linked immunosorbent assay kit. Results Mean serum level of calprotectin was significantly higher in the patients with AS compared with healthy controls (P = 0.003). Serum levels of calprotectin did not correlate with Bath AS disease activity index, AS disease activity score, Bath AS functional index, Bath AS radiology index, Bath AS metrology index, modified Schober, chest expansion, AS quality of life questionnaire, erythrocyte sedimentation rate, and C-reactive protein values (P > 0.05). Conclusions Our results suggest that calprotectin might play an important role in the pathogenetic mechanisms of AS; however, the calprotectin levels did not correlate with the measurements of disease activity, functional abilities, radiological damage, and the quality of life in these patients. Further insight into this area of research might provide opportunities to develop novel treatment strategies, which take into account the role of these peptides in the pathogenetic mechanisms of AS.
Circulating exosome microRNA associated with heart failure secondary to myxomatous mitral valve disease in a naturally occurring canine model

ABSTRACT Myxomatous mitral valve disease (MMVD) is functionally and histologically identical to mitral valve prolapse (MVP) in humans. Currently, there are no medical treatments that can delay the progression of this valvular disease or associated cardiac remodelling. Therefore, there is a need to understand the molecular pathology associated with MMVD and MVP better, and thus identify potential therapeutic targets. Circulating exosomes contain small RNA, including miRNA, which reflect cell physiology and pathology. This study explored the association between circulating exosomal miRNA (ex-miRNA) content and MMVD, heart failure due to MMVD (MMVD-CHF) and ageing, which is strongly associated with MMVD. Ex-miRNA was isolated from old normal/healthy dogs (n = 6), young normal dogs (n = 7), dogs with MMVD (n = 7) and dogs with MMVD-CHF (n = 7). Separately, total plasma miRNA was isolated from normal dogs (n = 8), dogs with MMVD (n = 8) and dogs with MMVD-CHF (n = 11). Using reverse transcription quantitative polymerase chain reaction, exosomal miR-181c (p = 0.003) and miR-495 (p = 0.0001) significantly increased in dogs with MMVD-CHF compared to the other three groups. Exosomal miR-9 (p = 0.002) increased in dogs with MMVD and MMVD-CHF compared to age-matched (old) normal dogs. Exosomal miR-599 (p = 0.002) decreased in dogs with MMVD compared to old normal dogs. In total plasma, 58 miRNA were deemed significantly different (p < 0.04) between normal dogs, dogs with MMVD and dogs with MMVD-CHF. However, in contrast to ex-miRNA, none of the miRNA in total plasma remained statistically significant if the false discovery rate was <15%. Changes in ex-miRNA are observed in dogs as they age (miR-9, miR-495 and miR-599), develop MMVD (miR-9 and miR-599) and progress from MMVD to CHF (miR-181c and miR-495). Ex-miRNA expression-level changes appear to be more specific to disease states than total plasma miRNA. RESPONSIBLE EDITOR Elena Aikawa, Harvard Medical School, USA
Bartonella Species in Fleas from Palestinian Territories: Prevalence and Genetic Diversity

ABSTRACT: Bartonellosis is an infectious bacterial disease. The prevalence and genetic characteristics of Bartonella spp. in fleas of wild and domestic animals from Palestinian territories are described. Flea samples (n=289) were collected from 121 cats, 135 dogs, 26 hyraxes and seven rats from northern (n=165), central (n=113), and southern Palestinian territories (n=11). The prevalent flea species were: Ctenocephalides felis (n=119/289; 41.2%), Ctenocephalides canis (n=159/289; 55%), and Xenopsylla sp. (n=7/289; 2.4%). Targeting the Intergenic Transcribed Spacer (ITS) locus, DNA of Bartonella was detected in 22% (64/289) of all fleas. Fifty percent of the C. felis and 57% of the Xenopsylla sp. contained Bartonella DNA. DNA sequencing showed the presence of Bartonella clarridgeiae (50%), Bartonella henselae (27%), and Bartonella koehlerae (3%) in C. felis. Xenopsylla sp. collected from Rattus rattus rats were infected with Bartonella tribocorum, Bartonella elizabethae, and Bartonella rochalimae. Phylogenetic sequence analysis using the 16S ribosomal RNA gene obtained four genetic clusters, B. henselae and B. koehlerae as subcluster 1, B. clarridgeiae as cluster 2, while the rat Bartonella species (B. tribocorum and B. elizabethae) were an outgroup cluster. These findings showed the important role of cat and rat fleas as vectors of zoonotic Bartonella species in Palestinian territories. It is hoped that this publication will raise awareness among physicians, veterinarians, and other health workers of the high prevalence of Bartonella spp. in fleas in Palestinian territories and the potential risk of these pathogens to humans and animals in this region.
The Fibromyalgia Impact Questionnaire: a useful tool in evaluating patients with post-Lyme disease syndrome.

OBJECTIVE To determine the reliability and validity of a modified version of the Fibromyalgia Impact Questionnaire (FIQ) in evaluating patients with post-Lyme disease syndrome (PLDS). METHODS In this cross-sectional analysis 13 PLDS, 18 fibromyalgia (FM), and 16 healthy controls (n = 47) completed a modified FIQ containing items to evaluate physical impairment, symptom severity, and global well-being. Comparisons between groups were done using analysis of variance with a significance level set at 0.05. RESULTS PLDS patients demonstrated statistically significantly greater levels of impairment than controls in physical functioning, FIQ total score, global well-being, joint pain, fatigue, depression, ability to perform activities of daily living, and memory/concentration. FM patients demonstrated a statistically significantly greater level of impairment than the control group in all categories, and the scores were significantly higher than the PLDS group in the measurement of physical impairment, FIQ total score, muscle pain, and joint pain. Overall, the instrument possesses good reliability and validity, although adequacy of this instrument to measure impairment in the male PLDS population needs further elucidation. CONCLUSION The results of this study suggest that the modified FIQ may be a useful tool in evaluating PLDS patients. The findings suggest that there may be some differences in the etiopathology of the symptoms experienced by PLDS and FM patients.
Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors.

PURPOSE This study evaluates the outcome of myeloablative chemotherapy and autologous bone marrow rescue (ABMR) with or without radiotherapy in children younger than 6 years of age with recurrent malignant brain tumors who had not previously been exposed to conventional fractionated external-beam irradiation. PATIENTS AND METHODS Patients underwent surgery and/or conventional chemotherapy at the time of recurrence to achieve minimal residual disease (two of these patients also underwent local single-fraction gamma-knife radiosurgery). Myeloablative chemotherapy was then administered with carboplatin, thiotepa, and etoposide (16 patients), thiotepa and etoposide (three patients), or thiotepa, etoposide, and carmustine (BCNU; one patient). Autologous bone marrow was re-infused 72 hours after chemotherapy. Twelve patients received external-beam irradiation after recovery from ABMR. RESULTS Twenty patients with recurrent brain tumors aged 0.7 to 5.9 years (median, 2.9 years) at ABMR were evaluated. Two patients died of toxicity related to myeloablative therapy. Eight patients died of progressive disease. Ten of 20 (50%) patients (primitive neuroectodermal tumor (PNET)/medulloblastoma, three patients; cerebral PNET, three patients; glioblastoma multiforme, two patients; anaplastic astrocytoma, one patient; pineal PNET, one patient) are alive and disease free at a median of 37.9 months (range, 9.7 to 98.2 months) from ABMR (3-year overall survival [OS] rate of 43% +/- 13% and event-free survival [EFS] rate of 47% +/- 14%]. Seven of these 10 patients also received irradiation post-ABMR. CONCLUSION Myeloablative chemotherapy with ABMR followed by additional external-beam irradiation appears to be an effective retrieval therapy for some young children with recurrent malignant brain tumors.
Comparison of methods to assess adherence to small-quantity lipid-based nutrient supplements (SQ-LNS) and dispersible tablets among young Burkinabé children participating in a community-based intervention trial.

Adherence to supplementation provided during an intervention trial can affect interpretation of study outcomes. We compared different approaches for estimating adherence to small-quantity lipid-based nutrient supplements (SQ-LNS) and dispersible tablets in a randomised clinical trial in Burkina Faso. A total of 2435 children (9-18 months) were randomly assigned to receive daily 20 g SQ-LNS with varying contents of zinc and a dispersible tablet containing 0 or 5 mg zinc. Adherence to SQ-LNS and tablets was assessed for all children through weekly caregiver interviews, and disappearance rate was calculated based on empty and unused packages returned during home visits. Additional adherence data were collected in different randomly selected subgroups of children: 12-h home observations were completed for children 11 and 16 months of age (n = 192) to assess consumption of SQ-LNS and dispersible tablets, and plasma zinc concentration was measured at baseline and 18 months (n = 310). Apparent adherence to SQ-LNS and dispersible tablets differed according to the assessment method used. Average daily caregiver-reported adherence to both SQ-LNS and dispersible tablets was 97 ± 6%. Disappearance rates showed similarly high average weekly adherence (98 ± 4%). In contrast, only 63% and 54% of children at 11 and 16 months, respectively, received SQ-LNS during the 12-h home observation periods, and fewer (32% and 27%) received a tablet. The lack of change in plasma zinc concentration after 9 months of supplementation suggests low adherence to the zinc tablet. Better methods are needed to assess adherence in community-based supplementation trials.
Development of disturbing dreams during adolescence and their relation to anxiety symptoms.

STUDY OBJECTIVES This work assesses the prevalence and development of disturbing dreams among adolescents and the association of these dreams with anxiety. DESIGN Sex differences in prevalence were analyzed with chi-square analyses. Changes over time were assessed with Wilcoxon tests and cross-tabulation tables. Associations with anxiety and DSM-III-R symptoms were assessed with ANOVA designs. SETTING N/A. PARTICIPANTS A total of 610 boys and girls rated their recall of disturbing and normal dreams at both 13 and 16 years of age. Subgroups of subjects were evaluated for anxiety symptoms at age 13 and for DSM-III-R symptoms of separation anxiety (SA), overanxious disorder (OD) and generalized anxiety disorder (GAD) at age 16. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS The recall of disturbing dreams was more prevalent for girls than for boys at both ages, and increased over time for girls while it decreased for boys. The recall of normal dreams was also more prevalent for girls at both ages, but this difference could not fully account for the difference in recall of disturbing dreams. Normal dream recall increased from age 13 to 16 for both sexes. The frequent occurrence of disturbing dreams was associated with anxiety at age 13 and with GAD, SA and OD symptoms at age 16 for both sexes. Evidence of more numerous OD symptoms for girls with frequent disturbing dreams suggests that this form of anxiety may partially account for the observed sex difference in disturbing dream prevalence. CONCLUSIONS The findings highlight a prevalence of disturbing dreams that is especially marked for adolescent girls. Unlike previous cross-sectional studies, which have found the same sex difference, this longitudinal design also calls attention to within-subjects changes in disturbing dream recall. The results also confirm that the frequent recall of disturbing dreams is associated with pathological symptoms of trait anxiety-apparently even as young as 13 years of age. Further study of disturbing dreams may contribute to understanding of associated pathophysiological factors which, too, vary by sex (e.g., PTSD, insomnia, depression).
Electroretinography of Wild-Type and Cry Mutant Mice Reveals Circadian Tuning of Photopic and Mesopic Retinal Responses

Attempts to understand circadian organization in the mammalian retina have concentrated increasingly on the mouse. However, rather little is known regarding circadian control of retinal light responses in this species. Here, the authors address this deficit using electroretinogram (ERG) recordings in C57BL/6 mice to evaluate rhythmicity in the wild-type retina and to identify the consequences of circadian clock loss in Cry1— /—Cry2—/— mice. They observe a circadian rhythm in the ERG waveform under light-adapted, cone-isolating conditions in wild-type mice, with b-wave speed and amplitude and the total power of oscillatory potentials all enhanced during the day. Wild types also exhibited a circadian dependence to ERG amplitude under dark-adapted conditions, but only when the flash stimulus was sufficiently bright to lie within the response range of cones. Cry1—/ —Cry2—/— mice lacked rhythmicity but retained superficially normal ERGs under all conditions suggesting that circadian clocks are dispensable for general retinal function. However, clock loss was associated with subtle abnormalities in retinal responses, with the amplitude of cone and mixed rod + cone ERGs constitutively enhanced. These data suggest that circadian clocks drive a fundamental fine-tuning of retinal pathways that is particularly apparent under conditions in which vision relies upon either cones alone or mixed rod + cone photoreception.
The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells

Background Naloxone is viewed as a specific competitive opioid antagonist acting at the level of opioid receptors (μ, δ, and κ) with blended agonist-adversary or agonist action. The role of naloxone in tumor cell growth has been poorly studied in human cancer cell lines. Materials and methods In the present study, we report findings from in vitro and in vivo experiments performed to evaluate the effects of naloxone on human breast cancer cell growth and progression. In vitro assays were conducted on estrogen receptor-negative human breast carcinoma cells, MDA.MB231, treated with naloxone at different concentrations (10–100 μM). In vivo experiments were performed on a mouse model of human triple-negative breast cancer generated by using MDA.MB231 injected subcutaneously in mice. Naloxone was daily intraperitoneally injected in mice at 0.357 mg/kg for 2 weeks and at 0.714 mg/kg for the next 2 weeks. Microvessels formation was detected by fluorescein isothiocyanate-dextran (100 μL) injected into the tail vein of mice and confirmed by immunohistochemistry with CD31 on mice tumor sections. Results In vitro tests showed that the cell proliferation of MDA.MB231 was inhibited by naloxone in a dose-dependent manner, whereas the cell death was increased. In vivo studies demonstrated that tumors of mice treated with naloxone were significantly smaller than those observed in the control groups, as long as naloxone was administered. Finally, naloxone was not able to impair the microvessel formation in tumors of treated mice. Conclusion Our data showed, for the first time, that naloxone reduced breast cancer progression without affecting angiogenesis.
Can ultrasonic energy efficiently speed 18O‐labeling of proteins?

We report in this work on the robustness of ultrasonic energy as a tool to speed the isotopic labeling of proteins using the 18O‐decoupling procedure. The first part of the decoupling procedure, comprising protein denaturation, reduction, alkylation and digestion, is done in 8 min under the effects of an ultrasonic field whilst the second part, the isotopic labeling, was assayed with and without the use of ultrasonic energy. Our results clearly demonstrate that the 18O‐isotopic labeling in a decoupling procedure cannot be accelerated using an ultrasonic field.
THE CHANGE IN QUANTITATIVE GENETIC VARIATION WITH INBREEDING

Abstract Inbreeding is known to reduce heterozygosity of neutral genetic markers, but its impact on quantitative genetic variation is debated. Theory predicts a linear decline in additive genetic variance (VA) with increasing inbreeding coefficient (F) when loci underlying the trait act additively, but a nonlinear hump-shaped relationship when dominance and epistasis are important. Predictions for heritability (h2) are similar, although the exact shape depends on the value of h2 in the absence of inbreeding. We located 22 published studies in which the level of genetic variation in experimentally inbred populations (measured by VA or h2) was compared with that in outbred control populations. For life-history traits, the data strongly supported a nonlinear change in genetic variation with increasing F. VA and h2 were, respectively, 244% and 50% higher at F = 0.4 than in outbred populations, and dominance plus epistatic variance together exceeded additive variance by a factor of four. For nonfitness traits the decline was linear and estimates of nonadditive variance were small. These results confirm that population bottlenecks frequently increase VA in some traits, and imply that life-history traits are underlain by substantial dominance or epistasis. However, the importance of drift-induced genetic variation in conservation or evolutionary biology is questionable, in part because inbreeding depression usually accompanies inbreeding.
Noisy Spiking in Visual Area V2 of Amblyopic Monkeys.

Interocular decorrelation of input signals in developing visual cortex can cause impaired binocular vision and amblyopia. While increased 'intrinsic noise' is thought to be responsible for a range of perceptual deficits in amblyopic humans, the neural basis for the elevated perceptual noise in amblyopic primates is not known. Here we tested the idea that perceptual noise is linked to the neuronal spiking noise (variability) resulting from developmental alterations in cortical circuitry. To assess spiking noise, we analyzed: the contrast dependent dynamics of spike counts and spiking irregularity by calculating the square of the coefficient of variation in inter spike intervals (CV2) and the trial-to-trial fluctuations in spiking (m-FF) in visual area V2 of monkeys reared with chronic monocular defocus. In 'amblyopic' neurons, the contrast vs. response functions and the spike count dynamics exhibited significant deviations from comparable data for normal monkeys. Spiking irregularity (CV2) was pronounced in amblyopic neurons for high contrast stimuli. The trial-to-trial variability in spiking (m-FF) was abnormally high in amblyopic neurons for low contrast gratings. The spike count, CV2, and m-FF of spontaneous activity were also elevated in amblyopic neurons. These contrast-dependent spiking irregularities were correlated with the level of binocular suppression in these V2 neurons and with the severity of perceptual loss for individual monkeys. Our results suggest that the developmental alterations in 'normalization' mechanisms, resulting from early binocular suppression, can explain much of these contrast-dependent spiking abnormalities in V2 neurons and the perceptual performance of our amblyopic monkeys. SIGNIFICANCE STATEMENT Amblyopia is a common developmental vision disorder in humans. Despite the extensive animal studies on how amblyopia emerges, we know surprisingly little about the neural basis of amblyopia in humans and non-human primates. While the vision of amblyopic humans is often described as being 'noisy' by perceptual and modeling studies, the exact nature or origin of this elevated perceptual noise is not known. We show that elevated and noisy spontaneous activity and contrast-dependent 'noisy spiking' (spiking irregularity and trial-to-trail fluctuations in spiking) in neurons of visual area (V2) could limit the visual performance of amblyopic primates. Moreover we discovered that the noisy spiking is linked to a high level of binocular suppression in visual cortex during development.