Saliva Viral Load Better Correlates with Clinical and Immunological Profiles in Children with Coronavirus Disease 2019

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 2020. NPS and saliva viral loads were correlated (r=0.315, p=0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r=-0.532, p<0.001) and saliva (r=-0.417, p<0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p<0.05), and were inversely correlated with total lymphocyte (r=-0.43), CD3 (r=-0.55), CD4 (r=-0.60), CD8 (r=-0.41), B (r=-0.482), and NK (r=-0.416) lymphocyte counts (all p<0.05). Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS

Prevalence and prognosis of myocardial scar in patients with known or suspected coronary artery disease and normal wall motion

<p>Abstract</p> <p>Background</p> <p>Some patients may have normal wall motion after myocardial infarction. The aim of this study was to determine the prevalence and prognosis of patients with myocardial scar in the absence of abnormal wall motion. We studied patients with suspected or known coronary artery disease (CAD) who were referred for cardiovascular magnetic resonance (CMR) for the assessment of global and regional cardiac function and late gadolinium enhancement (LGE) and had normal left ventricular wall motion. Prognostic value was determined by the occurrence of hard endpoints (cardiac death and nonfatal myocardial infarction) and major adverse cardiac events (MACE) which also included hospitalization due to unstable angina or heart failure or life threatening ventricular arrhythmia.</p> <p>Results</p> <p>A total 1148 patients (70.3%) were studied. LGE was detected in 104 patients (9.1%). Prevalence of LGE increased in patients with increased left ventricular mass. Average follow-up time was 955 ± 542 days. LGE was the strongest predictor for hard endpoints and MACE.</p> <p>Conclusion</p> <p>LGE was detected in 9.1% of patients with suspected or known CAD and normal wall motion. LGE was the strongest predictor of significant cardiac events.</p

Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: Experience of 370 consecutive cases

<p>Abstract</p> <p>Introduction</p> <p>To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy.</p> <p>Methods</p> <p>Between August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well.</p> <p>Results</p> <p>With a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (≤ 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications.</p> <p>Conclusion</p> <p>IMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.</p

Inhibition of HIV virus by neutralizing Vhh attached to dual functional liposomes encapsulating dapivirine

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations

Total hip arthroplasty: what information do we offer patients on websites of hospitals?

Contains fulltext : 97468.pdf (publisher's version ) (Open Access)BACKGROUND: Physicians face a new challenge; the self-educated patient. The internet is an important source that patients use to become self-educated. However, the individual choice for best treatment is difficult. The aim of this study was to investigate what kind of information is offered to total hip arthroplasty patients by internet and what information is appreciated by them. METHODS: Websites of orthopedic departments of all hospitals in the Netherlands were evaluated. In addition, a cohort of 102 patients, diagnosed with arthritic joint disorders, filled in an online survey and gave their opinion concerning the importance of this information. RESULTS: Eighty different orthopedic websites of hospitals were identified. Websites presented information regarding the orthopedic staff surgeon (76%) and the postoperative rehabilitation process (66%). They also offered referral to other orthopedic websites (61%), the opportunity to make an outpatient appointment (21%), and the opportunity to submit an online question (15%). Patients rated the presence of information regarding prosthesis survival as very important (>70%). However, the information on the type of prosthesis used by the hospital, and survival data of the prosthesis, were only present in ~9% and 5% respectively, of the websites. CONCLUSIONS: The content of health information on websites of hospitals is highly variable for total hip arthroplasty. Information regarding the hip implant and prosthesis survival is highly appreciated by patients, however, mostly absent on orthopedic websites in the Netherlands. The internet provides an enormous potential for orthopedic surgeons to inform the self-educated patient

Renal clearable catalytic gold nanoclusters for in vivo disease monitoring

Ultra-small gold nanoclusters (AuNCs) have emerged as agile probes for in vivo imaging, as they exhibit exceptional tumour accumulation and efficient renal clearance properties. However, their intrinsic catalytic activity, which can enable increased detection sensitivity, has yet to be explored for in vivo sensing. By exploiting the peroxidase-mimicking activity of AuNCs and the precise nanometer size filtration of the kidney, we designed multifunctional protease nanosensors that respond to disease microenvironments to produce a direct colorimetric urinary readout of disease state in less than 1 h. We monitored the catalytic activity of AuNCs in collected urine of a mouse model of colorectal cancer where tumour-bearing mice showed a 13-fold increase in colorimetric signal compared to healthy mice. Nanosensors were eliminated completely through hepatic and renal excretion within 4 weeks after injection with no evidence of toxicity. We envision that this modular approach will enable rapid detection of a diverse range of diseases by exploiting their specific enzymatic signatures

Higher-dimensional processing using a photonic tensor core with continuous-time data

This is the final version. Available from Nature Research via the DOI in this record. Data availability: The data that support the findings of this study are available from the corresponding author upon request. The ECG dataset analysed in this study is available from the open-source ‘Sudden Cardiac Death Holter Database’ via PhysioNet at https://doi.org/10.13026/C2W306. A sustainability report related to this article is available at https://nanoeng.materials.ox.ac.uk/sustainability.Code availability: The code used in the present work is available from the corresponding author upon request.New developments in hardware-based ‘accelerators’ range from electronic tensor cores and memristor-based arrays to photonic implementations. The goal of these approaches is to handle the exponentially growing computational load of machine learning, which currently requires the doubling of hardware capability approximately every 3.5 months. One solution is increasing the data dimensionality that is processable by such hardware. Although two-dimensional data processing by multiplexing space and wavelength has been previously reported, the use of three-dimensional processing has not yet been implemented in hardware. In this paper, we introduce the radio-frequency modulation of photonic signals to increase parallelization, adding an additional dimension to the data alongside spatially distributed non-volatile memories and wavelength multiplexing. We leverage higher-dimensional processing to configure such a system to an architecture compatible with edge computing frameworks. Our system achieves a parallelism of 100, two orders higher than implementations using only the spatial and wavelength degrees of freedom. We demonstrate this by performing a synchronous convolution of 100 clinical electrocardiogram signals from patients with cardiovascular diseases, and constructing a convolutional neural network capable of identifying patients at sudden death risk with 93.5% accuracy.European Union’s Horizon 2020European Union’s Innovation Council Pathfinder programmeSingapore A*STAR International Fellowshi

Impact of Visual Repetition Rate on Intrinsic Properties of Low Frequency Fluctuations in the Visual Network

BACKGROUND: Visual processing network is one of the functional networks which have been reliably identified to consistently exist in human resting brains. In our work, we focused on this network and investigated the intrinsic properties of low frequency (0.01-0.08 Hz) fluctuations (LFFs) during changes of visual stimuli. There were two main questions to be discussed in this study: intrinsic properties of LFFs regarding (1) interactions between visual stimuli and resting-state; (2) impact of repetition rate of visual stimuli. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed scanning sessions that contained rest and visual stimuli in various repetition rates with a novel method. The method included three numerical approaches involving ICA (Independent Component Analyses), fALFF (fractional Amplitude of Low Frequency Fluctuation), and Coherence, to respectively investigate the modulations of visual network pattern, low frequency fluctuation power, and interregional functional connectivity during changes of visual stimuli. We discovered when resting-state was replaced by visual stimuli, more areas were involved in visual processing, and both stronger low frequency fluctuations and higher interregional functional connectivity occurred in visual network. With changes of visual repetition rate, the number of areas which were involved in visual processing, low frequency fluctuation power, and interregional functional connectivity in this network were also modulated. CONCLUSIONS/SIGNIFICANCE: To combine the results of prior literatures and our discoveries, intrinsic properties of LFFs in visual network are altered not only by modulations of endogenous factors (eye-open or eye-closed condition; alcohol administration) and disordered behaviors (early blind), but also exogenous sensory stimuli (visual stimuli with various repetition rates). It demonstrates that the intrinsic properties of LFFs are valuable to represent physiological states of human brains