Summary Background Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte ...stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Methods Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group BILAG A organ domain score and no more than 1 new B organ domain score; and no worsening <0·3 increase in Physician's Global Assessment PGA score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00424476. Findings 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 51%, odds ratio 1·55 95% CI 1·10–2·19; p=0·0129) and 10 mg/kg (167 58%, 1·83 1·30–2·59; p=0·0006) than with placebo (125 44%) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 53%, 1·51 1·07–2·14; p=0·0189) and 10 mg/kg (169 58%, 1·71 1·21–2·41; p=0·0024) than with placebo (132 46%). More patients given belimumab 1 mg/kg (226 78%, 1·38 0·93–2·04; p=0·1064) and 10 mg/kg (236 81%, 1·62 1·09–2·42; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 73%). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 79%, 1·68 1·15–2·47; p=0·0078) and 10 mg/kg (231 80%, 1·74 1·18–2·55; p=0·0048) than with placebo (199 69%). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Interpretation Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Funding Human Genome Sciences and GlaxoSmithKline.
Objective
To examine emotion processing in euthymic bipolar patients (EBP) compared to healthy controls. In addition, to determine whether or not there is an association between emotion processing ...and psychosocial functioning.
Material and methods
A sample of 60 EBP and 60 healthy controls matched for age, gender, education level, and premorbid intelligence were studied. All subjects were assessed using the MATRICS Consensus Cognitive Battery (MCCB) and two additional executive function measures: the Trail Making Test‐Part B and the Stroop Test. Emotion processing was examined using the Mayer‐Salovey‐Caruso Emotional Intelligence Test (MSCEIT). Psychosocial functioning was assessed using the Functional Assessment Short Test (FAST).
Results
Euthymic bipolar patients obtained lower scores than controls in all MSCEIT measures except for the using emotions branch. Likewise, EBP obtained a worse performance than healthy controls in all neurocognitive domains. Correlation between MSCEIT strategic area measures and FAST total score was found (r = −0.311; P < 0.016). Regression analysis showed that residual depressive symptomatology explains a 9.1% of the variance in functional outcome. MSCEIT strategic area score explained an additional 8.6%. Neurocognition did not increase the percentage of the variance explained by emotion processing.
Conclusions
Euthymic bipolar patients exhibit deficits in emotion processing. Emotion processing is associated with social functioning in these patients.
Objective
Deficient prepulse inhibition (PPI) of the startle response, indicating sensorimotor gating deficits, has been reported in schizophrenia and other neuropsychiatric disorders. This study ...aimed to assess sensorimotor gating deficits in patients with euthymic bipolar. Furthermore, we analysed the relationships between PPI and clinical and cognitive measures.
Method
Prepulse inhibition was measured in 64 patients with euthymic bipolar and in 64 control subjects matched for age, gender, education level and smoking status. Clinical characteristics and level of functioning were assessed in all participants using Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST). Cognition was evaluated using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) and the Stroop test as an additional measure of executive function.
Results
Compared with controls, patients with bipolar disorder exhibited PPI deficits at 60‐ and 120‐millisecond prepulse–pulse intervals. Among patients with bipolar disorder, PPI was correlated with the social cognition domain of the MCCB. PPI was not significantly correlated with other clinical, functional and neurocognitive variables in either group.
Conclusions
Our data suggest that PPI deficit is a neurobiological marker in euthymic bipolar disorder, which is associated with social cognition but not with other clinical, functional or cognitive measures.
Objective
As in other health sciences, a career in dentistry is associated with numerous stressors in practitioners. The main objective of this research was to examine the prevalence of emotional ...exhaustion, burnout, and perceived stress among dental students in Mexico.
Methods
A cross-sectional study was conducted among 73 dental students attending a private university in Northern Mexico. Three scales were administered to students to identify emotional exhaustion, burnout, and perceived stress, and parametric data analysis was performed.
Results
Among participants (mean age 19.7 years), the proportion with emotional exhaustion, perceived high stress, and burnout was 52.0%, 42.3%, and 17.8%, respectively. All students with perceived stress also had burnout.
Conclusions
We found that emotional exhaustion and perceived stress are experienced by a large proportion of dentistry students enrolled in the third semester at this private university in Northern Mexico. The proportions were independent of age and sex.
Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and ...several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants.
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•Potent nAbs were isolated from an asymptomatic donor with low plasma neutralization•RBD-specific nAbs target epitopes overlapping with known RBD antibody classes•NTD mutations in B.1.1.7 Spike confer neutralization resistance to NTD-specific nAbs•Most RBD-specific nAbs retain potent neutralization of the B.1.1.7 variant
The impact of mutations arising in SARS-CoV-2 Spike on antigenicity is still not known. Graham et al. isolate potent neutralizing monoclonal antibodies from individuals experiencing a range of COVID-19 disease severity that target RBD, NTD, and non-S1 epitopes. The B.1.1.7 variant of concern was most resistant to NTD-specific nAbs whereas RBD-specific nAbs retained potent neutralization.
Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an ...interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included.
and
were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.
Abstract Epidemiological studies demonstrate an association between chronic consumption of arsenic contaminated water and cognitive deficits, especially when the exposure takes place during ...childhood. This study documents structural changes and nitrergic deficits in the striatum of adult female Wistar rats exposed to arsenic in drinking water (3 ppm, approximately 0.4 mg/kg per day) from gestation, throughout lactation and development until the age of 4 months. Kainic acid injected animals (10 mg/kg, i.p.) were also analyzed as positive controls of neural cell damage. Morphological characteristics of cells, fiber tracts and axons were analyzed by means of light microscopy as well as immunoreactivity to neuronal nitric oxide synthase (nNOS). As nitrergic markers, nitrite/nitrate concentrations, nNOS levels and expression of nNOS-mRNA were quantified in striatal tissue. Reactive oxygen species (ROS) and lipid peroxidation (LPx) were determined as oxidative stress markers. Arsenic exposure resulted in moderate to severe alterations of thickness, organization, surrounding space and shape of fiber tracts and axons, while cell bodies remained healthy. These anomalies were not accompanied by ROS and/or LPx increases. By contrast, except the expression of nNOS-mRNA, all nitrergic markers including striatal nNOS immunoreactivity presented a significant decrease. These results indicate that arsenic targets the central nitrergic system and disturbs brain structural organization at low exposure levels.
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