Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long ...COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.
In the head and neck, osteomas are the most common benign neoplasms of the nose and paranasal sinuses. They often form from the normal bone of the sinus cavities. The source of development of ...osteomas are unknown, though they are thought to arise from traumatic or infectious causes. Osteomas are often asymptomatic and detected incidentally, though larger osteomas may impart symptoms based on their mass effect. Whereas common within the nasal cavity and sinuses, osteomas arising from the external facial skeleton are exceedingly rare and not well described in the literature. Here we present a rare case of the diagnosis and surgical management of an osteoma of the zygoma.
•Osteomas are the most common benign tumors of the nose and paranasal sinuses.•Osteomas of the maxillofacial skeleton are exceedingly rare and poorly described in the literature.•Here we describe the diagnosis and surgical management of an osteoma of the zygoma.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has heavily mutated since the beginning of the coronavirus-2019 (COVID-19) pandemic. In this regard, the so-called variants of concern ...(VOCs) feature mutations that confer increased transmissibility and evasion of antibody responses. The VOCs have caused significant spikes in COVID-19 cases, raising significant concerns about whether COVID-19 vaccines will protect against current and future variants. In this context, whereas the protection COVID-19 vaccines offer against the acquisition of infection appears compromised, the protection against severe COVID-19 is maintained. From an immunologic standpoint, this is likely underpinned by the maintenance of T-cell responses against VOCs. Therefore, the role of T-cells is essential to understanding the broader adaptive immune response to COVID-19, which has the potential to shape public policies on vaccine protocols and inform future vaccine design. In this review, we survey the literature on the immunology of T-cell responses upon SARS-CoV-2 vaccination with the current FDA-approved and Emergency Use Authorized COVID-19 vaccines.
CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2 is an ...oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.
The current work presents a detailed investigation for the effect of a wide range friction stir welding (FSW) parameters on the dissimilar joints’ quality of aluminum alloys. Two groups of dissimilar ...weldments have been produced between AA5083/AA5754 and A5083/AA7020 using tool rotational rates range from 300 to 600 rpm, and tool traverse speeds range from 20 to 80 mm/min. In addition, the effect of reversing the position of the high strength alloy at the advancing side and at retreating side has been investigated. The produced joints have been investigated using macro examination, hardness testing and tensile testing. The results showed that sound joints are obtained at the low heat input FSW parameters investigated while increasing the heat input results in tunnel defects. The hardness profile obtained in the dissimilar AA5083/AA5754 joints is the typical FSW hardness profile of these alloys in which the hardness reduced in the nugget zone due to the loss of the cold deformation strengthening. However, the profile of the dissimilar AA5083/AA7020 showed increase in the hardness in the nugget due to the intimate mixing the high strength alloy with the low strength alloy. The sound joints in both groups of the dissimilar joints showed very high joint strength with efficiency up to 97 and 98%. Having the high strength alloy at the advancing side gives high joint strength and efficiency. Furthermore, the sound joints showed ductile fracture mechanism with clear dimple features mainly and significant plastic deformation occurred before fracture. Moreover, the fracture in these joints occurred in the base materials. On the other, the joints with tunnel defect showed some features of brittle fracture due to the acceleration of the existing crack propagation upon tensile loading.
This in vitro study evaluated the surface hydrophobicity of 3D-printed denture base resin exposed to either an extended post-curing light exposure time or a sandblasting procedure. MATERIALS AND ...METHODS: Disk-shaped samples (diameter × height: 10 mm × 3 mm) were 3D-printed with stereolithography SLA technology using the denture-base resin. Samples were divided into three groups: control, extended UV-post-curing, and sandblasted. The surface roughness parameters for each group were calculated, and the surface hydrophobicity was evaluated by measuring the drop contact angle. Analysis was done using the T-test; significance was when p < 0.05. RESULTS: The comparison of surface roughness parameters showed significant differences between the control group and the sandblasted group (Sa: p = 0.001, Sz: p < 0.001, Str: p < 0.001, Spc: p = 0.044) as well as between the extended-cure group and the sandblasted group (Sa: p = 0.006, Sz: p < 0.001, Str: p < 0.001, Spc: p = 0.036) except for the Sdr measures. The surface hydrophobicity was also statistically lower in the sandblasted group compared to both the control and extended curing groups (p < 0.001). CONCLUSION: The sandblasting procedure created a less hydrophobic surface of the 3D-printed denture base resin, and the altered surface roughness could be a contributor to this observation.
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•10-ns MD simulations were applied to model four protontation states of ASP32 and ASP228 of β-secretase.•The results show that the stable hydrogen bond network and structural ...stability in the HD32D228 model.•Docking studies show that the HD32D228 model gave the best enrich factor score.
β-secretase (BACE1) is an aspartyl protease that processes the β-amyloid peptide in the human brain in patients with Alzheimer’s disease. There are two catalytic aspartates (ASP32 and ASP228) in the active domain of BACE1. Although it is believed that the net charge of the Asp dyad is −1, the exact protonation state still remains a matter of debate. We carried out molecular dynamic (MD) simulations for the four protonation states of BACE1 proteins. We applied Glide docking studies to 21 BACE1 inhibitors against the MD extracted conformations. The dynamic results infer that the protein/ligand complex remains stable during the entire simulation course for HD32D228 model. The results show that the hydrogen bonds between the inhibitor and the Asp dyad are maintained in the 10,000th ps snapshot of HD32D228 model. Our results also reveal the significant loop residues in maintaining the active binding conformation in the HD32D228 model. Molecular docking results show that the HD32D228 model provided the best enrichment factor score, suggesting that this model was able to recognize the most active compounds. Our observations provide an evidence for the preference of the anionic state (HD32D228) in BACE1 binding site and are in accord with reported computational data. The protonation state study would provide significant information to assign the correct protonation state for structure-based drug design and docking studies targeting the BACE1 proteins as a tactic to develop potential AD inhibitors.
French Guiana is a multicultural overseas territory in the Amazon, where precariousness and difficulties in access to care are widespread. The prevalence of diabetes is double that of other French ...departments, and cardiovascular morbidity and mortality is high. The objective of the study was to analyze the biological, clinical and therapeutic follow-up of patients with diabetes mellitus using exhaustive data and to correlate it with national and European recommendations.
Using the national health insurance data, 9079 and 10075 patients with diabetes mellitus were analyzed in 2018 and 2019, respectively. We analyzed antidiabetic treatments, medical, dental, and podiatric consultations, examinations prescribed as part of the annual follow-up, and home nursing care.
There was a significant increase over one year in the number of patients (+10%) with diabetes, mainly women (60%), and 31% were under 54 years of age, with a disparity depending on the area of the territory, the most isolated having less access to screening. Less than 56% of patients had HbA1c measurements twice a year, less than 43% had an annual renal check-up, only 19% had an ophthalmic check-up at least every two years, less than 25% had an annual dental check-up, and less than 4% had an annual follow-up with the podiatrist.
Substandard diabetes monitoring is a major problem likely to increase morbidity and mortality. Adapting health care to the specificities of the territory is crucial, notably by formalizing the delegation of care to advanced practice nurse and non-healthcare professionals in precarious or geographically isolated areas.
In patients with heart failure with reduced ejection fraction (HFrEF), individual responses to beta-blockers vary. Candidate gene pharmacogenetic studies yielded significant but inconsistent results, ...and they may have missed important associations. Our objective was to use an unbiased genome-wide association study (GWAS) to identify loci influencing beta-blocker survival benefit in HFrEF patients. Genetic variant × beta-blocker exposure interactions were tested in Cox proportional hazards models for all-cause mortality stratified by self-identified race. The models were adjusted for clinical risk factors and propensity scores. A prospective HFrEF registry (469 black and 459 white patients) was used for discovery, and linkage disequilibrium (LD) clumped variants with a beta-blocker interaction of
< 5 × 10
, were tested for Bonferroni-corrected validation in a multicenter HFrEF clinical trial (288 black and 579 white patients). A total of 229 and 18 variants in black and white HFrEF patients, respectively, had interactions with beta-blocker exposure at
< 5 × 10
upon discovery. After LD-clumping, 100 variants and 4 variants in the black and white patients, respectively, remained for validation but none reached statistical significance. In conclusion, genetic variants of potential interest were identified in a discovery-based GWAS of beta-blocker survival benefit in HFrEF patients, but none were validated in an independent dataset. Larger cohorts or alternative approaches, such as polygenic scores, are needed.
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