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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Over the past months, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Various platforms are being used for the development of COVID-19 vaccine candidates recombinant viral vectors, protein-based vaccines, nucleic acid-based vaccines, and inactivated/attenuated virus. Recombinant viral vector vaccine candidates represent a significant part of those vaccine candidates in clinical development, with two already authorised for use in the European Union and one currently under rolling review by the European Medicines Agency (EMA). Since recombinant viral vector vaccine candidates are considered as genetically modified organisms (GMOs), their regulatory oversight includes besides an assessment of their quality, safety and efficacy, also an environmental risk assessment (ERA). The present article highlights the main characteristics of recombinant viral vector vaccine (candidates) against SARS-CoV-2 in the pipeline and discusses their features from an environmental risk point of view.There is a lack of studies investigating whether objectively measured physical activity (PA) and cardiorespiratory fitness (CRF) in puberty is associated with healthier body composition in late adolescence. The study sample included 71 boys, who were measured at puberty (mean age of 12.1 years) and again at late adolescence (mean age of 18.1 years). Physical activity was measured by accelerometry, and total PA, moderate-to-vigorous PA (MVPA), and sedentary time (SED) were calculated, while CRF was assessed by a peak oxygen consumption test. Body composition was measured by dual-energy X-ray absorptiometry, and body fat percentage (%BF), fat mass index (FMI), trunk fat mass index (TFMI), and fat-free mass index (FFMI) were calculated. Body mass index (BMI) and SED time increased, while MVPA, total PA, and CRF decreased from puberty to late adolescence. DNA Damage inhibitor A relatively high degree of tracking for BMI and CRF, and a low tracking for PA from puberty to late adolescence was observed. Only the CRF value at puberty negatively predicted adolescent BF% (β = -0.221; p = 0.015), FMI (β = -0.212; p = 0.006), and TFMI (β = -0.189; p = 0.015) values. Adolescents whose CRF was above the median at puberty had lower BMI, BF%, FMI, and TFMI in comparison to those whose CRF was below the median at puberty. In conclusion, measured CRF and PA values decreased from puberty to late adolescence. Pubertal CRF predicted body fatness indices six years later in healthy adolescents.Bone homeostasis plays a major role in supporting and protecting various organs as well as a body structure by maintaining the balance of activities of the osteoblasts and osteoclasts. Unbalanced differentiation and functions of these cells result in various skeletal diseases, such as osteoporosis, osteopetrosis, and Paget's disease. Although various synthetic nanomaterials have been developed for bone imaging and therapy through the chemical conjugation, they are associated with serious drawbacks, including heterogeneity and random orientation, in turn resulting in low efficiency. Here, we report the synthesis of bone-targeting ferritin nanoparticles for bone imaging. Ferritin, which is a globular protein composed of 24 subunits, was employed as a carrier molecule. Bone-targeting peptides that have been reported to specifically bind to osteoblast and hydroxyapatite were genetically fused to the N-terminus of the heavy subunit of human ferritin in such a way that the peptides faced outwards. Ferritin nanoparticles with fused bone-targeting peptides were also conjugated with fluorescent dyes to assess their binding ability using osteoblast imaging and a hydroxyapatite binding assay; the results showed their specific binding with osteoblasts and hydroxyapatite. Using in vivo analysis, a specific fluorescent signal from the lower limb was observed, demonstrating a highly selective affinity of the modified nanoparticles for the bone tissue. These promising results indicate a specific binding ability of the nanoscale targeting system to the bone tissue, which might potentially be used for bone disease therapy in future clinical applications.Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII-/- mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII-/- mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII-/- mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII-/- mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII-/- mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.
Patients requiring hospital care for COVID-19 may be stable for discharge soon after admission. This study sought to describe patient characteristics associated with short-stay hospitalization for COVID-19.
We performed a retrospective cohort study of patients with COVID-19 admitted to five United States hospitals from March to December 2020. We used multivariable logistic regression to identify patient characteristics associated with short hospital length-of-stay.
Of 3103 patients, 648 (20.9%) were hospitalized for less than 48 h. These patients were significantly less likely to have an age greater than 60, diabetes, chronic kidney disease; emergency department vital sign abnormalities, or abnormal initial diagnostic testing. For patients with no significant risk factors, the adjusted probability of short-stay hospitalization was 62.4% (95% CI 58.9-69.6).
Identification of candidates for early hospital discharge may allow hospitals to streamline throughput using protocols that optimize the efficiency of hospital care and coordinate post-discharge monitoring.
Identification of candidates for early hospital discharge may allow hospitals to streamline throughput using protocols that optimize the efficiency of hospital care and coordinate post-discharge monitoring.This paper studies a generalized version of multi-class cost-constrained random-coding ensemble with multiple auxiliary costs for the transmission of N correlated sources over an N-user multiple-access channel. For each user, the set of messages is partitioned into classes and codebooks are generated according to a distribution depending on the class index of the source message and under the constraint that the codewords satisfy a set of cost functions. Proper choices of the cost functions recover different coding schemes including message-dependent and message-independent versions of independent and identically distributed, independent conditionally distributed, constant-composition and conditional constant composition ensembles. The transmissibility region of the scheme is related to the Cover-El Gamal-Salehi region. A related family of correlated-source Gallager source exponent functions is also studied. The achievable exponents are compared for correlated and independent sources, both numerically and analytically.This paper examines the immature rupture of glass fiber reinforced plastic composite (GFRP) mitered elbow pipes. The GFRP composite mitered elbow pipe's lifespan was twenty-five years; however, the pipes in question experienced immature failures, resulting in the reduction of their lifetimes to seven, nine, and ten years, respectively. The GFRP cooling water mitered elbow pipe's service conditions operate at a pressure of up to 7 bar and temperatures between 15-36 °C. The root cause of failure was determined using visual inspection, analytical, microstructural, mechanical characterizations, and chemical analysis. The initial visualization inspection revealed an improper joint between the composite overwrapped and the straight pipe sections. Mechanical properties along the axial, hoop and 45° from the axial direction were obtained. The results from the analytical analysis indicated that the elbow might withstand the operating pressure depending on the quality factor, which was confirmed to be low due to the elbow joint's improper fabrication process. As evidence of this, the numerical analyses' results indicated that the safety factor in withstanding the operating pressure of 5 bar is dropped down in the radial region where the thickness is reduced to simulate the failure zone. This study's findings recommend that thickness of less than 15 mm be reinforced using overwrapped composites. It is recommended for future installations that the fabrication process be appropriately monitored and controlled and avoids using 45°/-45° fiber orientation and multiple layers of chopped strand mat glass fiber.
Thyroid-stimulating hormone (TSH) suppression therapy is an important treatment modality for differentiated thyroid carcinoma (DTC), but it increases fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and trabecular bone score (TBS) in postmenopausal DTC patients receiving TSH suppression therapy.
A total of 410 postmenopausal DTC patients who underwent thyroidectomy and had at least two dual-energy X-ray absorptiometry measurements, including a preoperative measurement, were included. Patients who had osteoporosis medication for more than 1 year were classified as 'patients with osteoporosis'.
In patients without osteoporosis, the change in %BMD was similar between TSH suppression (-) and (+) groups, while the decrease in %TBS was significantly greater in the TSH suppression (+) group than that of the TSH suppression (-) group. The relative risk of vertebral fracture was decreased by TBS changes but not by BMD changes. In patients with osteoporosis, both BMD and TBS showed significant increases in the TSH suppression (-) group but not in TSH suppression (+) group. At year 4, TBS was significantly lower in the TSH suppression (+) group than that in the TSH suppression (-) group, while BMD showed no difference between groups.
TBS may better reflect bone health than BMD in postmenopausal DTC patients with TSH suppression therapy.
TBS may better reflect bone health than BMD in postmenopausal DTC patients with TSH suppression therapy.