Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucose impairs B‐1 cell function in diabetes

B‐1 lymphocytes produce natural immunoglobulin (Ig)M, among which a large proportion is directed against apoptotic cells and altered self‐antigens, such as modified low‐density lipoprotein (LDL). Thereby, natural IgM maintains homeostasis in the body and is also protective against atherosclerosis. Diabetic patients have an increased risk of developing certain infections as well as atherosclerosis compared with healthy subjects, but the underlying reason is not known. The aim of this study was to investigate whether diabetes and insulin resistance affects B‐1 lymphocytes and their production of natural IgM. We found that diabetic db/db mice had lower levels of peritoneal B‐1a cells in the steady state‐condition compared to controls. Also, activation of B‐1 cells with the Toll‐like receptor (TLR)‐4 agonist Kdo2‐Lipid A or immunization against Streptococcus pneumoniae led to a blunted IgM response in the diabetic db/db mice. In‐vitro experiments with isolated B‐1 cells showed that high concentrations of glucose, but not insulin or leptin, caused a reduced secretion of total IgM and copper‐oxidized (CuOx)‐LDL‐ and malondialdehyde (MDA)‐LDL‐specific IgM from B‐1 cells in addition to a decreased differentiation into antibody‐producing cells, proliferation arrest and increased apoptosis. These results suggest that metabolic regulation of B‐1 cells is of importance for the understanding of the role of this cell type in life‐style‐related conditions.
Frequency of parent-reported indicators of sleep disordered breathing in children with clinical diagnosis of adenotonsillar hypertrophy in Benin City, Nigeria.

Background: Sleep disordered breathing (SDB) comprises a wide spectrum of sleep-associated breathing abnormalities; those related to increase upper airway resistance include snoring, upper airway resistance syndrome (UARS) and obstructive sleep apnea syndrome (OSAS). This concept suggests that a person who snores may be exhibiting the first manifestation of SDB and that snoring should not be viewed as normal. Obstructive sleep disordered breathing is common in children. Snoring, mouth breathing, and obstructive sleep apnea (OSA) often prompt parents to seek medical attention. Aim: This study aims to determine the frequency of parent-reported indicators of SDB among Original Research Article Onyeagwara et al.; BJMMR, 9(10): 1-9, 2015; Article no.BJMMR. 19026 2 children clinically diagnosed with adenotonsilar hypertrophy (ATH) in the Otorhinolaryngology department of the University of Benin Teaching Hospital (UBTH), Benin City. Methods: This was a cross-sectional study of children aged 12 years and below who were sent to the Ear Nose and Throat clinics of UBTH, Benin-city with symptoms of obstructive adenotonsilar hypertrophy (ATH) between May 2012 and April 2014. All consecutive parent/caregiver who presented their child/ward to the ENT clinic with symptoms of obstructive adenotonsilar hypertrophy (ATH) were interviewed using structured questionnaire/proforma after verbal consent was obtained. Results: A total of 104 children were studied. The children were 73 males and 31 females with a male/ female ratio of 2.4:1. The children were aged 1-12yrs with average age of 4.98 ± 2.68 years. The parents/caregivers were 92 females and 12 males giving a ratio of 7.6:1.The frequency of sleep apnea was reported by 50 children/care givers (48.1%). There was a high prevalence of reporting for patients between the ages of 1 and 4years 62 (59.6%) which was followed by those between 5 and 9 years 34 (32.7%). Symptoms lasted more than 3 years in 43(41.3%), 1-2 years in 31(29.9%) and less than 1 year in 30 (28.8%) of the patients. Symptoms reported were snoring 104 (100%), nasal obstruction 97(93%), nasal discharge 96 (92%), mouth breathing 92 (88%), sleep apnea 50 (48.1%), restless night sleep 72 (69.2%), sore throat 69(66.3%), failure to thrive 2(1.9%). Cervical (jugulo-digastric) lymph node was enlarged in 70 (67.3%). Tonsillar grades were as follows; grade 3 was 59 (56.7%), 4 was 27 (26%) while 1 and 2 accounted for 17 (16.3%). Conclusion: Snoring was the commonest symptom reported in children with SDB. Parents and caregivers should monitor their children closely during sleep as this may reveal early symptoms of adenotonsilar hypertrophy causing SDB.
Preventing potentially inappropriate medication use in hospitalized older patients with a computerized provider order entry warning system.

BACKGROUND Potentially inappropriate medication (PIM) use in hospitalized older patients is common. Our objective was to determine whether a computerized provider order entry (CPOE) drug warning system can decrease orders for PIMs in hospitalized older patients. METHODS We used a prospective before-and-after design among patients 65 years or older admitted to a large, urban academic medical center in Boston, Massachusetts, from June 1, 2004, through November 29, 2004 (for patients admitted before the warning system was added), and from March 17, 2005, through August 30, 2008 (patients admitted after the warning system was added). We instituted a medication-specific warning system within CPOE that alerted ordering providers at the point of care when ordering a PIM and that advised alternative medication or dose reduction. The main outcome measure was the rate of orders for PIMs before and after the warning system was deployed. RESULTS The mean (SE) rate of ordering medications that were not recommended dropped from 11.56 (0.36) to 9.94 (0.12) orders per day after the implementation of a CPOE warning system (difference, 1.62 [0.33]; P<.001), with no evidence that the effect waned over time. There were no appreciable changes in the rate of ordering medications for which only dose reduction was recommended or that were not targeted after CPOE implementation. These effects persisted in autoregressive models that accounted for secular trends and season (P<.001). CONCLUSION Specific alerts embedded into a CPOE system, used in patients 65 years or older, can decrease the number of orders of PIMs quickly and specifically.
When aging does not increase distraction: Evidence from pure auditory and visual oddball tasks.

Past research indicates that age increases deviance distraction in cross-modal oddball tasks, but results are few and less conclusive in purely auditory oddball tasks, with 3 studies not reporting age-related increase in deviance distraction against 1 that did (d = 1.04). This study aimed to (a) examine the effect of age on deviance distraction using the largest sample size to date to ensure adequate statistical power and (b) extend the study of same-modality deviance distraction to the visual modality. We compared 42 young and 42 older adults in auditory and visual duration discrimination tasks in which stimuli were presented with rare and unexpected task-irrelevant changes in pitch (in the auditory task) or location (in the visual task). The statistical power of our experiment to detect an effect size (d) of 1.04 was . 999. Our results showed deviance distraction (longer response times for deviant stimuli than for standard stimuli) in both modalities. Importantly, these effects did not vary with age. Strong support for the absence of age-related variation in deviance distraction was further demonstrated by Bayes factor analysis. We conclude that aging does not appear to increase behavioral distraction by deviant stimuli in same-modality oddball tasks.
Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy.

BACKGROUND Polypharmacy and inappropriate medication use is a problem in elderly patients, who are more likely to experience adverse effects from multiple treatments and less likely to obtain the same therapeutic benefit as younger populations. The Good Palliative-Geriatric Practice algorithm for drug discontinuation has been shown to be effective in reducing polypharmacy and improving mortality and morbidity in nursing home inpatients. This study reports the feasibility of this approach in community-dwelling older patients. METHODS The Good Palliative-Geriatric Practice algorithm was applied to a cohort of 70 community-dwelling older patients to recommend drug discontinuations. Success rates of discontinuation, morbidity, mortality, and changes in health status were recorded. RESULTS The mean (SD) age of the 70 patients was 82.8 (6.9) years. Forty-three patients (61%) had 3 or more and 26% had 5 or more comorbidities. The mean follow-up was 19 months. Participants used a mean (SD) of 7.7 (3.7) medications. Protocol indicated that discontinuation was recommended for 311 medications in 64 patients (58% of drugs; mean [SD], 4.4 [2.5] drugs per patient overall, 4.9 per patient who had discontinuation). Of the discontinued drug therapies, 2% were restarted because of recurrence of the original indication. Taking nonconsent and failures together, successful discontinuation was achieved in 81%. Ten elderly patients (14%) died after a mean follow-up of 13 months, with the mean age at death of 89 years. No significant adverse events or deaths were attributable to discontinuation, and 88% of patients reported global improvement in health. CONCLUSIONS It is feasible to decrease medication burden in community-dwelling elderly patients. This tool would be suitable for larger randomized controlled trials in different clinical settings.
A clinical solution to antimicrobial resistance in community-acquired pneumonia: narrowing the spectrum of antimicrobial therapy: comment on "Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial t

F or several generations, infectious disease specialists have sounded a clarion warning of impending antimicrobial agent resistance. That forewarning has been fulfilled for community-acquired pneumonia (CAP). Streptococcus pneumoniae, the leading pathogen in CAP, has become resistant to the penicillins (in vitro), macrolides, and quinolones. The wellpublicized nonavailability of new antimicrobial agents aggravates this ominous trend. The pharmaceutical industry has been reluctant to invest large sums of money to overcome the hurdles of academic institutional review boards and the US Food and Drug Administration (FDA). But a solution is at hand. Instead of developing new antimicrobial agents, we should halt the widespread practice of antibiotic empiricism. Fortuitously, the age of innovative technology and molecular laboratory testing has also arrived. The application of new clinical microbiology tests to identify the offending pathogen may allow administration of narrow spectrum antibiotic therapy. In the article by Sordé et al in this issue of the Archives, the pneumococcal urinary antigen was shown to be effective in identifying S pneumoniae, and for 75% of patients diagnosed as having pneumococcal pneumonia, it was the only test result that was positive. This is pertinent given the practical difficulties of obtaining adequate sputum for culture and Gram stain. Rapid turnaround time allows the clinician to use targeted rather than empirical therapy for the pneumoccoccus shortly after examining the patient. Add the Gram stain of sputum, another rapid test, and the clinician has 2 potent diagnostic tests that should allow the use of penicillin for pneumococcal pneumonia rather than the oft-used regimen of either a quinolone or a combination of thirdgeneration cephalosporin plus a macrolide.
Alpha‐melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus‐like model

Alpha‐melanocyte stimulating hormone (α‐MSH) is a neuropeptide exhibiting anti‐inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α‐MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α‐MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α‐MSH analogue [Nle4, DPhe7]‐α‐MSH (NDP–MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti‐nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α‐smooth muscle actin (α‐SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin‐releasing factor (CRF) and α‐MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)‐6, IL‐10, proteinuria and mesangial cell proliferation together with glomerular expression of α‐SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP‐MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP–MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α‐SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α‐MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.
Distress tolerance treatment for inner -city drug users: A preliminary trial

Title: DISTRESS TOLERANCE TREATMENT FOR INNER-CITY DRUG USERS: A PRELIMINARY TRIAL Marina Alexa Bornovalova, Ph.D., 2008 Directed By: Carl W. Lejuez, Associate Professor, Department of Psychology Despite advances in preventing treatment failure, a large percentage of substanceusing individuals drop out of treatment. Current work indicates that one’s threshold for tolerating psychological distress (i.e., distress tolerance) is a key factor in treatment dropout. Following from this work, we developed a treatment for prevention of treatment drop-out in a residential treatment setting. Specifically 66 individuals who were a) receiving residential substance use treatment and b) evidenced deficits in distress tolerance at a baseline assessment were assigned to receive either the novel treatment (Skills for Improving Distress Intolerance, SIDI), supportive counseling (SC) treatment, or no-treatment control (NTC). We hypothesized that compared to individuals in the SC and NTC, individuals in the SIDI would show greater improvements in levels of distress tolerance, greater improvement on measures theoretically related to distress tolerance (i.e., levels of negative affect, disengagement coping, emotion regulation, self-efficacy in high-risk situations, and self-efficacy of mood regulation), and higher rates of treatment completion. Results indicated that those in SIDI evidenced greater improvement in distress tolerance, compared to SC and NTC. However, there were no significant differences in improvement in the secondary measures, except for affect regulation self-efficacy (approaching significance). It should be noted, however, that the percentage of individuals reaching clinically significant improvement showed that more individuals in SIDI, compared to SC and NTC, reached such improvement. Comparison of 30-day treatment completion showed that there were no dropouts in either SIDI or SC; all dropouts occurred in NTC. When considering dropout throughout the entire residential treatment contract (ranging from 30 to 180 days), the least dropouts occurred in SIDI, followed by SC and NTC (in this order); however, this difference was not significant. The current results suggest that SIDI is effective in increasing distress tolerance in inner-city drug users. Additionally, the variable rates of dropout that were, nevertheless, nonsiginficant suggest a need for larger-scale studies to test the effect of SIDI on dropout. DISTRESS TOLERANCE TREATMENT FOR INNER-CITY DRUG USERS: A PRELIMINARY TRIAL.
Multisensory Cue Combination After Sensory Loss: Audio-Visual Localization in Patients With Progressive Retinal Disease

Human adults can combine perceptual estimates from different senses to minimize uncertainty, by taking a reliability-weighted average (the maximum likelihood estimate, MLE). Although research has shown that healthy human adults reweight estimates as their reliability changes from one trial to the next, less is known about how humans adapt to gradual long-term changes in sensory reliability. This study assessed whether individuals diagnosed with progressive visual deterioration, due to retinal disease, combined auditory and visual cues to location according to optimal (MLE) predictions. Twelve patients with central visual loss, 10 patients with peripheral visual loss, and 12 normally sighted adults were asked to localize visual and/or auditory targets in central (1°–18°) and peripheral (36°–53°) locations. Normally sighted adults and patients with peripheral visual loss showed multisensory uncertainty reduction and cue weighting in line with MLE predictions. In contrast, patients with central visual loss did not weight estimates appropriately in either the center or the periphery, and failed to meet MLE predictions in the periphery. Our results show that one visual loss patient group succeeded at optimal cue combination, whereas the other patient group (patients with central vision loss) did not. We propose that sensory remapping due to changes in fixation behavior may contribute to apparent failures in the latter group.
Influenza vaccination and vitamin K antagonist treatment: a placebo-controlled, randomized, double-blind crossover study.

BACKGROUND Among millions of persons vaccinated against influenza virus each year, many are older patients treated with several drugs, including vitamin K antagonists (VKAs), among which warfarin is the most commonly used. Due to high interpatient and intrapatient variability, the therapeutic dose of VKA has to be individualized by monitoring of international normalized ratio (INR) values. The objectives of this study were to evaluate variation in the INR and warfarin weekly dose variation after influenza vaccination administration and to follow up patients for related hemorrhagic and thrombotic events to evaluate the safety of the influenza vaccine and to assess the immunogenicity of the influenza vaccination in patients receiving VKAs. METHODS One hundred four patients on a stable VKA regimen and with an indication for influenza vaccination were randomized to receive influenza vaccination and subsequent placebo administration, or vice versa. All patients were tested for coagulation variables, clinical events, and antibody response against vaccine components. RESULTS Similar mean prothrombin times, expressed as the INR and VKA weekly dose, were found in patients after receiving vaccine or placebo. The absence of any vaccination effect on VKA treatment was confirmed using a linear mixed-effects model. The percentages of time that patients were in therapeutic range were 70.7% after receiving vaccine and 72.4% after receiving placebo (P = .57). There were no fatal or major bleeding events and 11 minor mucocutaneous hemorrhagic events. After vaccination, the percentage of seroprotected patients ranged from 92.0% to 100.0% depending on the vaccine antigen examined. CONCLUSIONS Influenza vaccination had no significant effect on INR values or warfarin sodium weekly doses. Close monitoring of INR values is not required after influenza vaccination in patients on stable long-term VKA regimens. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00222638.
Distinct Cognitive Control Mechanisms as Revealed by Modality-Specific Conflict Adaptation Effects

Cognitive control is essential to resolve conflict in stimulus-response compatibility (SRC) tasks. The SRC effect in the current trial is reduced after an incongruent trial as compared with a congruent trial, a phenomenon being termed conflict adaptation (CA). The CA effect is found to be domain-specific, such that it occurs when adjacent trials contain the same type of conflict, but disappears when the conflicts are of different types. Similar patterns have been observed when tasks involve different modalities, but the modality-specific effect may have been confounded by task switching. In the current study, we investigated whether or not cognitive control could transfer across auditory and visual conflicts when task-switching was controlled. Participants were asked to respond to a visual or auditory (Experiments 1A/B) stimulus, with conflict coming from either the same or a different modality. CA effects showed modality-specific patterns. To account for potential confounding effects caused by differences in task-irrelevant properties, we specifically examined the influence of task-irrelevant properties on CA effects within the visual modality (Experiments 2A/B). Significant CA effects were observed across different conflicts from distinct task-irrelevant properties, ruling out that the lack of cross-modal CA effects in Experiments 1A/B resulted from differences in task-irrelevant information. Task-irrelevant properties were further matched in Experiments 3A/B to examine the pure effect of modality. Results replicated Experiments 1A/B showing robust modality-specific CA effects. Taken together, we provide supporting evidences that modality affects cognitive control in conflict resolution, which should be taken into account in theories of cognitive control.
Self-Relevance Prioritizes Access to Visual Awareness

As we are cognizant of only a fraction of the available visual inputs at any given time, how is information selected for access to consciousness? In particular, does the personal significance of stimuli influence perceptual selection? Given that self-relevant information is prioritized during various stages of processing, here we hypothesized that self-association may privilege access to awareness under continuous flash suppression (CFS). The results supported this prediction. Compared with geometric shapes referenced to either a friend or stranger, those previously associated with self were prioritized in visual awareness. To establish the basis of this effect, the processes underlying task performance were investigated using a hierarchical drift diffusion model approach. These analyses showed that self-prioritization mapped onto both the decisional (i.e., starting value, z) and nondecisional (i.e., t0) parameters of the diffusion model. The implications of these findings are considered.