Validation of the self-management ability scale (SMAS) and development and validation of a shorter scale (SMAS-S) among older patients shortly after hospitalisation

Background  

The 30-item Self-Management Ability Scale (SMAS) measures self-management abilities (SMA). Objectives of this study were to (1) validate the SMAS among older people shortly after hospitalisation and (2) shorten the SMAS while maintaining adequate validity and reliability.     

Body size at birth modifies the effect of fat mass and obesity associated (FTO) rs9939609 polymorphism on adiposity in adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

The present study was intended to examine whether ponderal index (PI) at birth modifies the effect of the fat mass and obesity associated (FTO) rs9939609 polymorphism on adiposity in European adolescents. A total of 628 adolescents aged 14·4 (se 1·3) years (56·8 % female) were recruited. PI was calculated from parental reports of birth weight and length (kg/m3), and the BMI (kg/m2), body fat percentage and fat mass index (FMI, kg/m2) were calculated. The rs9939609 polymorphism was genotyped and physical activity assessed by accelerometry. Sex, duration of pregnancy, pubertal status, centre and physical activity were used as confounders in all the analyses. The minor A allele of the FTO rs9939609 was significantly associated with higher BMI, body fat percentage and FMI (all P < 0·05) but not with PI. Significant interactions between PI and the rs9939609 polymorphism in terms of body fat percentage (P = 0·002) and FMI (P = 0·017) were detected. However, this polymorphism was only significantly associated with higher BMI, body fat percentage and FMI (all P < 0·05) in adolescents in the lower PI tertile. Indeed, both body fat percentage and FMI were higher in those adolescents in the lower PI tertile carrying the A allele of the FTO rs9939609 polymorphism than in those with the TT genotype (25·0 (se 0·8) v. 22·1 (se 1·0) %, adjusted P = 0·030 and 5·6 (se 0·3) v. 4·6 (se 0·4) kg/m2, P = 0·031, respectively). Our findings suggest that those adolescents born with lower PI could be more vulnerable to the influence of the A risk allele of the FTO polymorphism on total adiposity content.     

Prolonged acute migraine with aura and reversible brain MRI abnormalities after liquid sclerotherapy

Transient visual disturbances constitute the most commonly reported neurological side effect during and immediately after sclerotherapy. A few studies, based on clinical and diffusion-weighted MRI assessments, have suggested that these transient neurological symptoms correspond to migraine with aura. Recently, it has been reported that brain magnetic resonance imaging can reveal transient T2*-weighted abnormalities during the acute phase of migraine with aura. We reported a 36-year-old man who presented with transient neurological symptoms and concomitant T2*-weighted abnormalities on brain magnetic resonance imaging immediately after liquid sclerotherapy. We hypothesize that the reversible nature of the patient’s T2*-weighted abnormalities may indicate a relationship with the post-sclerotherapy migraine with aura attack.     

Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.     

Attention searches nonuniformly in space and in time

Difficult search tasks are known to involve attentional resources, but the spatiotemporal behavior of attention remains unknown. Are multiple search targets processed in sequence or in parallel? We developed an innovative methodology to solve this notoriously difficult problem. Observers performed a difficult search task during which two probes were flashed at varying delays. Performance in reporting probes at each location was considered a measure of attentional deployment. By solving a second-degree equation, we determined the probability of probe report at the most and least attended probe locations on each trial. Because these values differed significantly, we conclude that attention was focused on one stimulus or subgroup of stimuli at a time, and not divided uniformly among all search stimuli. Furthermore, this deployment was modulated periodically over time at ∼7 Hz. These results provide evidence for a nonuniform spatiotemporal deployment of attention during difficult search.Visual search tasks (e.g., to find a target embedded among similar looking distracters) have long been used to investigate the deployment of attention (1–6). Certain tasks are performed “efficiently,” in which case the search time and accuracy are independent of the number of distracters. Other tasks are more difficult, or “inefficient,” characterized by an increase in reaction times (RTs) and/or a decrease in accuracy with the number of distracting elements, a result typically attributed to the need to allocate attention (4–7). For more than 30 y now, since the pioneering study of Treisman and Gelade in 1980 (4), two opposing theories of attention deployment during difficult search have persisted. Attention could either be allocated nonuniformly to the stimuli, such that in some cases it would switch sequentially from one stimulus (or group of stimuli) to another (4, 5), or be divided uniformly to process all of the stimuli in parallel, but with a drop in efficiency for increasing distractor numbers (2, 8–10). To date, neither of these two theories has been unequivocally disproved. Overall performance in the search task itself is not directly informative, because both theories predict an increase in RT with the number of distracters (11, 12). One alternative is to use briefly flashed probes to test for the deployment of attention at a specific location and time. With two probes, it should be possible to differentiate parallel and sequential processing strategies: The strict parallel theory predicts that both probes should receive equal amounts of attention, whereas the sequential theory predicts that one of the probes will receive more attention than the other. Of course, the most attended probe may not be the same one on every trial, but a simple mathematical manipulation, the solution of a quadratic equation, allows us to access this information despite the need to average performance over trials.In recent years, a second, related, debate has arisen in the literature concerning the temporal behavior of attention. It has been proposed that attention samples visual stimuli periodically rather than continuously (13–18). This question is connected to the uniform vs. nonuniform debate in that the nonuniform (or sequential) model of attention processing maps rather naturally onto a periodic sampling of visual information (with the periodicity reflecting the switching between stimuli). No such relation exists for the parallel uniform model, making it more naturally compatible with continuous processing (although, of course, not incompatible with periodic sampling arising for independent reasons).Consequently, in this study, we asked whether attention processing during a difficult search task is uniform or nonuniform, both in space and in time. We used a difficult (attention demanding) visual search task consisting of finding a letter T among letter L’s (four stimuli). After a varying delay, we probed two of the four stimulus locations (Fig. 1) and computed performance in reporting both probes correctly (PBOTH) or none of the probes correctly (PNONE). Using the mathematical manipulation described in Methods, we were able to determine that attention was not divided equally between the four search item positions, but focused on one stimulus or subgroup of stimuli at a time. Moreover, we found that the deployment of attention was modulated periodically at theta frequency (∼7 Hz). We conclude that in this difficult search task, attention was deployed nonuniformly both in space and in time.Open in a separate windowFig. 1.Experimental procedure. One second to 2 s after pressing the space bar, the search array appears for 30–200 ms depending on the randomly chosen SOA for this trial. Observers report the presence or absence of the target stimulus T among distracting L letters. After the variable SOA (from 30–450 ms relative to search array onset), two probe letters appear randomly for 80 ms at two of the four search array locations. For probe onset SOAs greater than 200 ms, an additional empty screen is presented between the search task and the probe detection task (the fixation point is maintained). In other words, if the SOA was shorter than 200 ms, the interstimulus interval (ISI) was zero; otherwise, the ISI was greater than zero. Masks follow probe stimuli for 200 ms. After mask offset, observers first report the presence or absence of the T among L’s, and then the identity of the two probe stimuli by selecting letters from a list, using the computer mouse. A trial ends when observers click on the end button.     

From the Cover: Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus

Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emergent subgroup C betacoronavirus that was detected for the first times in June and September of 2012, when two cases of severe infections were identified in the Eastern Mediterranean region (1, 2). As of June 29, 2015, 1,379 human infections with 531 deaths have been confirmed in 26 countries in the Middle East, Europe, North Africa, Asia, and Americas, including the recent outbreak in South Korea caused by an individual who traveled to the Middle East, which caused 164 infections and 23 deaths (www.ecdc.europa.eu). MERS-CoV causes severe infection of the lower respiratory tract, similar to the Severe Acute Respiratory Syndrome CoV (SARS-CoV) that appeared in China in 2002. Several cases of human-to-human transmission have been reported in health care workers and family clusters, but at the current time there is no evidence of sustained human-to-human transmission.SARS-CoV and MERS-CoV belong to the B and C betacoronavirus lineages and have been shown to bind to cellular receptors ACE2 and CD26 [also known as dipeptidyl peptidase 4 (DPP4)], respectively. Of note, SARS-CoV targets ciliated bronchial epithelial cells and type I and type II pneumocytes, whereas MERS-CoV infects type II pneumocytes and nonciliated bronchial cells. These differences might account for the different rates of human-to-human transmission, which was high for SARS-CoV and is moderate to low for MERS-CoV. The two viruses differ also in the duration of their epidemic, which was limited for SARS-CoV (from November 2002 to July 2003) and long-lasting for MERS-CoV, which appeared in 2012 and continues to circulate in the Middle East.As to the zoonotic reservoir, both MERS-CoV and SARS-CoV probably originated in bats (3, 4) with dromedary camels serving as intermediate hosts for the human MERS-CoV infection and palm civets and raccoon dogs for SARS-CoV (5). Dromedary camels have a close association with humans in the affected areas. Of note, whereas in humans MERS-CoV infects the lower respiratory tract, rendering human-to-human transmission inefficient, in camels the virus infects the upper respiratory tract and is present in nasal secretions at high concentrations, which favors transmission to humans and other camels. However, the mechanisms of transmission from camels to humans and from humans to humans as well as the global incidence in humans are still unclear. Camels show no or mild symptoms, and antibodies found in banked sera samples show that the virus has been present in the animals for at least the past 20 y (6). In addition, most of the patients described appeared to have been infected in hospitals, from other MERS patients, and even many of those who became infected outside a hospital report no exposure to camels. Recent epidemiological data suggest that more than ∼45,000 people in Saudi Arabia were seropositive for a MERS infection, implying that the majority of infections may not detected, the case fatality rate is lower than current estimates of about 40%, or significant levels of unreported severe disease have been misdiagnosed over the past 5–20 y.The trimeric S protein of MERS-CoV mediates receptor binding and membrane fusion and is the major target for neutralizing antibodies (7, 8). The structure of the cellular receptor (CD26), which is conserved across many species (9), and the complex of CD26 with the receptor binding domain (RBD) of the S protein have been determined by X-ray crystallography (10, 11).Recently, two groups have used nonimmune human antibody-phage display libraries to isolate neutralizing antibodies to MERS-CoV (12, 13). The antibody 3B11 described by Tang et al. (12) showed neutralizing activity against some but not all strains. m336, a second antibody described more recently by Ying et al. (13), showed high neutralizing potency and used the same VH gene (i.e., VH1-69) with high homology to 3B11 in the HCDR3, suggesting that the two antibodies might have a similar mode of interaction. This hypothesis is supported by the analysis of m336 escape mutants. Here we describe for the first time, to our knowledge, the isolation of a potent neutralizing human monoclonal antibody from the memory B cells of an infected patient that might be developed for the prevention and treatment of MERS-CoV infections.     

IMQ‐induced skin inflammation in mice is dependent on IL‐1R1 and MyD88 signaling but independent of the NLRP3 inflammasome

The pathogenesis of inflammatory skin diseases such as psoriasis involves the release of numerous proinflammatory cytokines, including members of the IL‐1 family. Here we report overexpression of IL‐1α, IL‐1β, and IL‐1 receptor antagonist mRNA, associated to expression of IL‐23p19, IL‐17A, and IL‐22 in skin cells, upon topical application of the TLR7 agonist imiquimod (IMQ) in C57BL/6J mice. IMQ‐induced skin inflammation was partially reduced in mice deficient for both IL‐1α/IL‐1β or for IL‐1 receptor type 1 (IL‐1R1), but not in IL‐1α‐ or IL‐1β‐deficient mice, demonstrating the redundant activity of IL‐1α and IL‐1β for skin inflammation. NLRP3 or apoptosis‐associated Speck‐like protein containing a Caspase recruitment domain‐deficient mice had no significant reduction of skin inflammation in response to IMQ treatment, mainly due to the redundancy of IL‐1α. However, IMQ‐induced skin inflammation was abolished in the absence of MyD88, the adaptor protein shared by IL‐1R and TLR signaling pathways. These results are consistent with the TLR7 dependence of IMQ‐induced skin inflammation. Thus, IL‐1R1 contributes to the IMQ‐induced skin inflammation, and disruption of MyD88 signaling completely abrogates this response.     

Hemoglobin North Shore: a variant hemoglobin associated with the phenotype of beta-thalassemia

Hemoglobin (Hb) North Shore (beta 134 val leads to glu) is a mutant hemoglobin that is associated with the phenotype of mild heterozygous beta-thalassemia. Heterozygotes are characterized low normal hemoglobin levels or mild anemia, microcytosis, increased HbA2, and 34%-38% Hb North Shore. The mechanism of the anemia and microcytosis associated with Hb North Shore was explored by studies of hemolysate thermal instability, peripheral blood globin biosynthesis, and whole blood oxygen affinity. Hb North Shore was mildly heat unstable in comparison to normal adult hemolysate. Pulse labeling of reticulocytes with 3H- leucine showed an alpha/beta ratio of 1.35 (normal 1.0). The beta North Shore/alpha ratio was 0.22-0.27, which was less than expected on the basis of gene dosage and less than that seen for most beta-chain variants. The beta A/alpha ratio was 0.50, as would be expected. The beta North Shore/alpha ratio was 0.26 after a 15-min pulse and did not decrease during 120 min of chase. These findings suggest that suboptimal synthesis rather than posttranslational degradation is responsible for the thalassemic phenotype associated with this variant hemoglobin. These observations parallel the findings in heterozygous HbE. It is not presently known whether the thalassemia phenotype is conferred by the structural mutation itself or by another mutation cis to the beta North Shore gene.