Three-dimensional printing of porous load-bearing bioceramic scaffolds

This article reports on the use of the binder jetting three-dimensional printing process combined with sintering to process bioceramic materials to form micro- and macroporous three-dimensional structures. Three different glass-ceramic formulations, apatite–wollastonite and two silicate-based glasses, have been processed using this route to create porous structures which have Young’s modulus equivalent to cortical bone and average bending strengths in the range 24–36 MPa. It is demonstrated that a range of macroporous geometries can be created with accuracies of ±0.25 mm over length scales up to 40 mm. Hot-stage microscopy is a valuable tool in the definition of processing parameters for the sintering step of the process. Overall, it is concluded that binder jetting followed by sintering offers a versatile process for the manufacture of load-bearing bioceramic components for bone replacement applications

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function

Effect of different finishing and polishing systems on surface properties of universal single shade resin-based composites

Abstract Background Recently, universal single-shade resin composites have become increasingly available in the dental market. The modification of their composition can have an inadvertent effect on their physical and surface properties, and subsequently determinantal effect on their clinical function and longevity. Therefore, this study aimed to evaluate the effect of different finishing and polishing (F/P) systems on surface roughness (Ra), surface gloss (GU), and Vickers microhardness (VMH) of universal single-shade RBCs. Materials and methods Four commercial RBCs were used; the universal single-shade RBCs were Omnichroma, Charisma® Diamond ONE, and Vittra APS Unique, and a conventional nanocomposite Filtek™ Z250 XT was used as a control. The 3 F/P systems were Sof-Lex™ XT, Enhance®/PoGo®, and Diacomp® Plus Twist. A total of 160 discs were used for the 3 F/P system groups for all RBCs (n = 10). After F/P, the Ra, GU, and VMH were assessed. The data were analyzed using 2-way ANOVA at p-value < 0.05. Results Significant differences were found among the four RBCs and the 3 F/P systems (p < .000). Omnichroma showed the lowest Ra and acceptable GU, but the lowest VMH. Charisma showed the highest Ra, acceptable GU, and VMH. Vittra showed acceptable Ra, GU, and VMH and Filtek showed the highest GU, VMH, and acceptable Ra. Conclusion Although conventional nanohybrid RBC (Filtek Z250 XT) showed better GU and VMH values, the universal single-shade RBCs demonstrated comparable surface properties. The highest GU & VMH and lowest Ra were achieved by Diacomp followed by Enhance and Soflex

Case Series: Sacubitril/Valsartan Role for Chemotherapy-Induced Cardiotoxicity: An in-Depth Investigation in Saudi Arabia

Abdullah Alshammari,1 Basmah Ahmed Qasem,1 Nouf Ahmed Almatrafi,1 Lujain Mofareh Alharbi,1 Abeer Abdulhadi Alhuthali Snr,2 Attiah Abdulrahman Khobrani,2 Mohammed Alnuhait1 1Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Clinical Pharmacy Department, King Abdullah Medical City, Makkah, Saudi ArabiaCorrespondence: Mohammed Alnuhait, Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia, Email [email protected]: Chemotherapy-induced cardiotoxicity is a significant problem, ranking as the second most frequent cause of mortality in cancer patients. This adverse outcome encompasses many cardiovascular problems, such as heart failure. Sacubitril/valsartan has shown potential in the management of heart failure, however, its effectiveness in treating chemotherapy-induced heart failure has not been extensively explored. We performed a case series to investigate the safety and effectiveness of sacubitril/valsartan in treating chemotherapy-induced cardiomyopathy in Saudi Arabia.Methods: The case series was conducted at a single medical center in Makkah, Saudi Arabia. The data gathered included patient demographics, clinical features, laboratory results, echocardiographic findings, and medication information. The data underwent analysis using descriptive statistics.Results: Out of the total of eight patients who were part of the investigation, a notable majority of six individuals exhibited substantial enhancements in their ejection fraction (EF) after receiving sacubitril/valsartan medication.Conclusion: Our case series provides significant insights by revealing improvements in ejection fraction (EF) in six out of eight patients who had chemotherapy-induced cardiomyopathy after receiving sacubitril/valsartan treatment.Keywords: oncology, sacubitril/valsartan, cardiotoxicity, chemotherapy, Saudi Arabi

Euphorbiasteroid Abrogates EGFR and Wnt/β-Catenin Signaling in Non-Small-Cell Lung Cancer Cells to Impart Anticancer Activity

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3βS9 with a parallel increase in β-TrCP and phosphorylation of GSK-3βY216. Lithium chloride treatment increased the phosphorylation of GSK-3βS9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells

A Cross-Sectional Analysis into the Willingness and Hesitancy to Test and Vaccinate Against COVID-19 Among the Elderly Population in the Kingdom of Saudi Arabia

Reem S AlOmar,1 Nouf A AlShamlan,1 Marwa Mahmoud Shafey,1 Assim M AlAbdulKader,1 Khalid S AlHarkan,1 Wejdan M Al-Johani,1 Sameerah Motabgani,1 Nourah K Alkaltham,1 Abdullah A Alharbi2 1Department of Family and Community Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Family and Community Medicine Department, Faculty of Medicine, Jazan University, Jazan City, Jazan, Saudi ArabiaCorrespondence: Reem S AlOmar, Email [email protected]: COVID-19 remains a public health concern. Vaccinations, testing and tracing have been proven to provide strong protection against severe illness and death. Older adults are amongst the groups with an increased risk of severe illness. This study aimed to explore the willingness and hesitancy of the elderly population in the Kingdom of Saudi Arabia to test and vaccinate against COVID-19.Methods: This cross-sectional study targeted participants aged 65 years and above. The questionnaire included both sociodemographic variables, and variables related to willingness and hesitancy to vaccinate and test for COVID-19 that were mainly based on existing literature. Bivariate analyses were performed to test for associations. Significance was set at the 0.05 level.Results: The total sample of respondents was 502. The results show that 52.4% were not aware of a previous infection. Participants aged above 70 years and females were found to be more aware of a previous infection (51.6% and 53.1% respectively) (P < 0.05). Also, 54.7% felt it necessary to test against COVID-19, and among those, 70.8% believed that testing would contain and control the spread. The results also show that 3.2% were not vaccinated to date, compared to 95.41% who had the complete dose as well as the recommended booster dose for elderlies. Age, sex and level of education were significantly associated with vaccine uptake, where participants aged between 65 and 70 years, males and high levels of education were associated with a complete vaccine uptake.Discussion: The current findings add to the epidemiological evidence and show that the social network theory within the context of health may have played a role in self-awareness of previous infections. Also, social factors should be incorporated in public health interventions and public health campaigns targeting the elderly are still needed especially with the continued discovery of variants of interests.Keywords: COVID-19, public health, health promotion, prevention, elderl