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3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design. [ABSTRACT FROM AUTHOR]

Background: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) Methods: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. Results: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7–18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). Conclusions: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: − 0.99 g/L; 95% CI, − 1.11 to − 0.88, p < 0.001). In multivariate meta-regression analysis, age (t = − 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t = − 2.77, p = 0.008) and C-reactive protein (t = − 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group. [ABSTRACT FROM AUTHOR]

Purpose: To present our experience of cases of pulmonary sarcoidosis with atypical HRCT patterns found during 2016 focusing on the differential diagnosis to contribute to the difficult role of the radiologist in the disease identification and to help the clinicians to reach the diagnosis.Materials and methods: The HRCT examinations of 47 patients with sarcoidosis were studied retrospectively. All patients had a histopathological confirm of the disease. 29 (61.7%) show a typical pulmonary pattern and 18 (38.3%) an atypical pattern. The latter were evaluated by three experienced radiologists dedicated to thoracic disease to radiologically define the predominant pattern of presentation.Results: In the 18 patients (38.3%) with atypical sarcoidosis, the following parenchymal patterns were observed: four patients (22.2%) had interstitial fibrotic alterations, three patients (16.6%) with reticular pattern with inter–intralobular septal thickening, two patients (11.1%) with small-airway involvement with mosaic oligoemia, two patients (11.1%) with pleural involvement (pneumothorax and pleural plaques), one patient (5.5%) with fibrocystic changes, 1 (5.5%) with halo-sign, 1 (5.5%) with diffuse bilateral ground-glass opacities, and 1 (5.5%) with isolated lung mass; in addition, three patients (16.6%) with atypical lymph node pattern were also found.Conclusions and Discussion: The atypical pulmonary alterations found in CT examination can be confused with other lung diseases and they are always a challenge even for the most experienced radiologist. In our experience, cases with atypical pulmonary sarcoidosis patterns evaluated in the study are consistent with similar cases described in the literature, both in lymph node and atypical parenchymal involvement. All the atypical characteristics of the work should alert the radiologist to consider sarcoidosis among the possible differential diagnoses, always correlating the results of the computed tomography examination with appropriate clinical-laboratory evaluations. [ABSTRACT FROM AUTHOR]

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration. [ABSTRACT FROM AUTHOR]

For a long time, the endothelial covering of the vessels has been considered an inert surface. On the contrary, the endothelial cells are active and dynamic elements in the interaction between blood and tissues. The control of the vessel basal tone is obtained by the complex balance between the relaxing and contracting endothelial factors. Previous clinical studies show that patients suffering from rheumatoid arthritis and other autoimmune rheumatologic pathologies are at high risk of death being prematurely affected by atherosclerosis and cardiovascular diseases. Blocking tumor necrosis factor (TNF)-α by biological drugs improves the endothelial function. The aim of our study was to evaluate the effects of two anti-TNF-α drugs (infliximab and etanercept) on the endothelial function by evaluating the flow-mediated dilatation (FMD), which was measured in the brachial artery before and after treatment and after 8-12 weeks. We enrolled 36 patients (average age 52 ± 9.8 years, 12 men and 24 women), 25 of them were affected by rheumatoid arthritis (RA) and 11 were affected by psoriatic arthritis (PsA) and they were divided into three groups: 10 patients were treated with etanercept, 13 patients were treated with infliximab, 13 patients were treated with DMARDs. We measured the common carotid intimal-medial thickness (ccIMT) and the endothelial function was evaluated by FMD measurement in the brachial artery, before treatment, 1 h after the beginning of treatment and after 8-12 weeks. No statistically significant difference between the three groups was found for the ultrasonographic evaluation of the carotid IMT. On the contrary, the differences between FMD values before and after the treatment in the patients treated with etanercept (13.1 ± 0.01 vs. 18.8 ± 0.01%, p < 0.01) and in the patients treated with infliximab (11.8 ± 0.09 vs. 16.7 ± 0.09%, p < 0.01) were statistically significant. Long-term evaluation for infliximab and etanercept was performed by comparing the FMD values, respectively, 8 and 12 weeks after the first treatment. After 8 weeks, FMD value was similar to the value recorded at enrollment in the infliximab group (11.9 ± 0.03 vs. 13.54 ± 0.04%, p = 0.236) and the FMD values in the etanercept group after 12 weeks showed a not statistically significant reduction of vasodilatating effect (13.01 ± 0.03 vs. 15.67 ± 0.02%, p = 0.197). In conclusion, the use of biological drugs in patients affected by autoimmune arthritis can modify the endothelial function, as indicated by the induced FMD changes, but the long-term effect tends to be considerably reduced. [ABSTRACT FROM AUTHOR]

Population ageing and improved healthcare may lead to an increase in the prevalence of stroke. The aim of this study is to investigate the prevalence of stroke and stroke-related disability in a population sample resident in Aosta, Italy. The information was collect using a simple questionnaire for first ever stroke in the past combined with the analysis of the patients’ medical records and integrated with the information reported by six general practitioners. 102 cases of stroke were identified in the study population of 6,930 subjects, for an overall prevalence per 1,000 inhabitants of 1.4 (95% CI 0.81–1.99), which increased to 4.79 (95% CI 3.29–6.29) in subjects aged ≥65 years. Fifty-nine percent of the cases were completely or partially dependent (Rankin scores of 2–5). At the time of interview, 72% were living at home. Our data do not reveal any increase in the prevalence of stroke, possibly because of a reduced incidence of the disease. [ABSTRACT FROM AUTHOR]

Lightweight multifunctional electromagnetic (EM) absorbing materials with outstanding thermal properties, chemical resistance and mechanical stability are crucial for space, aerospace and electronic devices and packaging. Therefore, 3D porous graphene aerogels are attracting ever growing interest. In this paper we present a cost effective lightweight 3D porous graphene-based aerogel for EM wave absorption, constituted by a poly vinylidene fluoride (PVDF) polymer matrix filled with graphene nanoplatelets (GNPs) and we show that the thermal, electrical, mechanical properties of the aerogel can be tuned through the proper selection of the processing temperature, controlled either at 65 °C or 85 °C. The produced GNP-filled aerogels are characterized by exceptional EM properties, allowing the production of absorbers with 9.2 GHz and 6.4 GHz qualified bandwidths with reflection coefficients below −10 dB and −20 dB, respectively. Moreover, such aerogels show exceptional thermal conductivities without any appreciable volume change after temperature variations. Finally, depending on the process parameters, it is shown the possibility to obtain water repellent aerogel composites, thus preventing their EM and thermal properties from being affected by environmental humidity and allowing the realization of EM absorber with a stable response. [ABSTRACT FROM AUTHOR]