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The recent emergence of SARS-CoV-2 variants of concern1-10 and the recurrent spillovers of coronaviruses11,12 into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses.
Establishing a professional identity in nursing is integral to professional development, yet this area of inquiry remains understudied.
This segment of a multiphased national study measured nursing faculty's perceived level of importance regarding key components of professional identity in nursing using the newly developed Professional Identity in Nursing Survey (PINS).
Fifty subject matter experts from nursing education, practice, and regulation utilized the DeVellis scale development process to develop the PINS over the course of 2 years. Nearly 1200 nurse educators evaluated the importance of a 34-item scale relating to professional identity in nursing.
At endorsement of 95% or greater, 28 items were found to be important components of nursing identity. Effective communication, integrity, and being trustworthy and respectful were reported as most important to nursing identity.
Nurse educators identified the important items to assess professional identity in nursing. Item refinement and psychometric evaluation of the survey are the next phase of the multiphased study.
Nurse educators identified the important items to assess professional identity in nursing. Item refinement and psychometric evaluation of the survey are the next phase of the multiphased study.
International guideline recommendations on safe use of contrast media (CM) are conflicting regarding the necessity to prewarm iodinated CM.
Aim of the study was to evaluate the effects of room temperature CM compared with prewarmed CM on image quality, safety, and patient comfort in abdominal computed tomography (CT).
CATCHY (Contrast Media Temperature and Patient Comfort in Computed Tomography of the Abdomen) is a double-blinded, randomized noninferiority trial. Between February and August 2020, 218 participants referred for portal venous abdominal CT were prospectively and randomly assigned to 1 of 2 groups. All patients received iopromide at 300 mg I/mL group 1 at room temperature (~23°C [~73°F]) and group 2 prewarmed to body temperature (37°C [99°F]). A state-of-the-art individualized CM injection protocol was used, based on body weight and adapted to tube voltage. Primary outcome was absolute difference in mean liver attenuation between groups, calculated with a 2-sided 95% confidence interval. Ther in abdominal CT imaging. Prewarming conferred no beneficial effect on image quality, safety, and comfort, and might therefore no longer be considered a prerequisite in state-of-the art injection protocols for parenchymal imaging.
Not prewarming iodinated CM was found noninferior in abdominal CT imaging. Prewarming conferred no beneficial effect on image quality, safety, and comfort, and might therefore no longer be considered a prerequisite in state-of-the art injection protocols for parenchymal imaging.
Fixation-off sensitivity (FOS) is a discharge pattern on EEG that occurs owing to the loss of central vision or fixation. Knowledge regarding the relationship between FOS and symptomatic epilepsy is limited. Therefore, we aimed to evaluate the electroclinical features of FOS in adult patients with symptomatic epilepsy.
Outpatient video-EEG records of the Hacettepe University Faculty of Medicine were reviewed from 2009 to 2019. Patients aged >18 years with symptomatic epilepsy with a FOS pattern were included. Demographic, clinical, EEG, and neuroimaging data were retrospectively evaluated from an electronic database and patient files.
Eight patients (50% female) were included in this study; seven (87%) had refractory epilepsy. Prominent risk factors were family history of epilepsy in five patients and prenatal/natal insult in four patients. Notable MRI signs included cortical developmental malformation, posterior gliosis, and frontoparietal porencephalic cyst. The FOS pattern was generalized with posmplicated than previously thought.
The follow-up and monitoring of response to immunomodulatory therapy in patients with chronic inflammatory demyelinating polyneuropathy are still challenging. Various outcome measures have been proposed in recent years, and some are now frequently used in daily clinical practice; however, reliable biomarkers for the disease activity and treatment response are lacking.
Cross-sectional nerve area of the bilateral vagus, fifth and the sixth cervical spinal, median, ulnar, tibial, peroneal, and sural nerves were measured at 2 time points with an interval of 6 months using nerve ultrasound. The results were used to calculate the ultrasound pattern sumscore (UPSS). The correlation between UPSS change (ΔUPSS) and changes in functional and nerve conduction studies measures over the study period were assessed.
Sixteen patients completed this prospective, observational study. General linear model showed that ΔUPSS is significantly associated with ΔMedical Research Council sumscore (β = -0.72, P = 0.003), Δhandgrip strength (β = -0.57, P = 0.014), ΔRasch-built overall disability scale (β = -0.57, P = 0.010), and Δoverall neuropathy limitations scale (β = 0.75, P < 0.001), after adjustment of confounding variables. Nevertheless, ΔUPSS was not correlated with other clinical measures, including Δpinch power, Δ9-hole peg test, Δ10-m walking test, and Δnerve conduction study sumscore (P values > 0.05).
Nerve ultrasound might be an efficient method for monitoring the functional status of patients with chronic inflammatory demyelinating polyneuropathy over time because the alterations in its scores could significantly reflect clinical changes.
Nerve ultrasound might be an efficient method for monitoring the functional status of patients with chronic inflammatory demyelinating polyneuropathy over time because the alterations in its scores could significantly reflect clinical changes.
A dysfunction of beta oscillatory activity is the neurophysiological hallmark of Parkinson disease (PD). How cortical activity reacts to external perturbations may provide insight into pathophysiological mechanisms. This study aims at identifying modifications in EEG rhythms after transcranial magnetic stimulation (TMS) in PD. We hypothesize that single-pulse TMS can modulate brain intrinsic oscillatory properties (e.g., beta excess).
EEG data were coregistered during single-pulse TMS (100 stimuli over the primary motor cortex [M1, hotspot for Abductor Pollicis Brevis], random intertrial interval from 8 to 13 seconds). We used a time-frequency analysis based on wavelet method to characterize modification of oscillatory rhythms (delta [1-4 Hz], theta [4-7 Hz], alpha [8-12 Hz], and beta [13-30 Hz] in 15 participants with PD compared with 10 healthy controls.
An increase in beta power over the sensorimotor areas was recorded at rest in the PD group (P < 0.05). Brain oscillations in PD transiently reset after TMS beta power over M1 becomes comparable to that recorded in aged-matched healthy subjects in the 2 seconds following TMS.
Transcranial magnetic stimulation over the dominant motor cortex transiently normalizes cortical oscillations. More user-friendly noninvasive brain stimulation needs to be trialed, based on this proof of concept, to provide practical, portable techniques to treat motor symptoms in PD.
Transcranial magnetic stimulation over the dominant motor cortex transiently normalizes cortical oscillations. More user-friendly noninvasive brain stimulation needs to be trialed, based on this proof of concept, to provide practical, portable techniques to treat motor symptoms in PD.Pheochromocytomas are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. They may occur sporadically or in the context of hereditary syndromes. All pheochromocytomas are considered to have malignant potential (defined as risk of metastasis, not local invasion). The use of grading systems with incorporated clinical and histopathologic parameters can help but not definitively predict the metastatic potential of pheochromocytomas. The recent discovery of susceptibility genes provided new insights into the pathogenesis and introduced additional approaches to estimate the metastatic risk of pheochromocytoma. Eeyarestatin 1 concentration However, the prevalence of these genetic signatures in pheochromocytomas has yet to be fully addressed. Therefore, in the present study, we retrospectively reviewed cases of pheochromocytoma from 1980 to 2018 in the archives of our institution. Three hundred ninety cases were identified, and their clinicopathologic characteristics and genetic statuses were analyzed. About 25% of the cases had metastases, which were more common in older patients (median, 49 y) than in younger ones. Univariate and multivariate analyses revealed that older age, Hispanic ethnicity, metastasis, and large primary tumor size were markedly associated with poor overall survival. In contrast, family history of pheochromocytoma, lack of symptoms, and bilateral adrenal involvement were associated with better survival. About 37% of the pheochromocytomas were associated with inherited syndromes. About 52% of tested patients had pathogenic mutations of pheochromocytoma susceptibility genes. Of these, succinate dehydrogenase B gene mutation had the strongest association with metastasis. These data support that genetic testing should be offered to all patients with pheochromocytoma.
High blood pressure (HBP) in children causes pre-clinical damage to the heart and accelerates atherosclerosis. Current pharmacological treatments have limited ability to prevent end-organ damage, particularly that of the kidneys. A contrasting element between adult vs. pediatric HPB treatment, is the emphasis in adults on exercise regimens that target increments in cardiorespiratory fitness [CRF, (peak VO2)]. The aim of this study was to evaluate the association of CRF with blood pressure percentiles and blood pressure status in children with normal and excessive adiposity (NA vs. EA). An exploratory aim was to measure associations of CRF with a) other cardiovascular disease risk factors commonly found in children with HBP, and b) kidney function.
Children (n= 211), attended one study visit. CRF was measured using an incremental bike test, and body composition by dual-energy X-ray absorptiometry. Fat-free mass (FFM) index was calculated as kilograms of fat-free mass per square meter. Multiple logistic and linear regression analyses were used to model the probability of HBP, and other variables of interest [plasma lipids, HOMA2-IR, ALT, and glomerular filtration rate (eGRF)] against peak VO2.
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