Κυριακή 16 Οκτωβρίου 2022

Persistence of Neutrophil extracellular traps and anti‐cardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

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Abstract

This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in non-severe (NS), severe (S) and post-acute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097 and 0.64; 0.99, 1.0 and 0.82; and 0.94, 1.0, and 0.93, in NS, S and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs (Neutrophil extracellular traps) markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate post-acute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.

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Characteristics and clinical significance of plasma IL‐18, sCD14 and sCD163 levels in patients with HIV‐1 infection

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Abstract

Background and aim

Biomarkers of monocyte-macrophages activation and inflammation in plasma such as interleukin-18 (IL-18), soluble leukocyte differentiation antigen 14 (sCD14) and sCD163 are associated with disease severity and prognosis in HIV-1 infected patients, however, their relationships with efficacy of antiretroviral therapy (ART) need further investigation. We aimed to characterize and explore the clinical significance of plasma IL-18, sCD14 and sCD163 in this population.

Methods

This was a retrospective cohort study consisting of HIV-1 infected patients enrolled in a randomized, controlled, open-label, non-inferiority trial (ALTERLL study), with follow-up time points including initiation of ART (baseline), 12-, 24- and 48-weeks of treatment. Plasma levels of IL-18, sCD14 and sCD163 were measured using enzyme-linked immunosorbent assay method. Viral suppression was defined as HIV-1 RNA <20 copies/mL.

Results

Among the 193 studied pa tients (median age of 29.0 years, 180 males), IL-18 and sCD163 had U-shaped regression curves and sCD14 had an inverted U-shaped regression curve while virus was decreasing and immune function recovered. Patients with higher levels of IL-18 or lower levels of sCD163 at baseline were less likely to achieve viral suppression at week 12 or week 24 of treatment, respectively. In multivariate analysis, baseline sCD163 ≤500 pg/mL (aOR 0.33, 95%CI 0.16-0.68) was independently associated with lower rate of viral suppression at week 24 of treatment.

Conclusion

We demonstrated different dynamic changes among IL-18, sCD14 and sCD163 after ART. Baseline sCD163 level could be a potential predictor of early virological response to ART. Further validation and mechanistic research are needed.

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Characterization and application of a series of monoclonal antibodies against SARS‐CoV‐2 nucleocapsid protein

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Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic has a significant global social and economic impact, and the emergence of new and more destructive mutant strains highlights the need for accurate virus detection. Here, 90 monoclonal antibodies (MAbs) that exclusively reacted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP) were generated. These MAbs did not cross-react with NPs of common human coronaviruses (HCoV, i.e., 229E, OC43, HKU1, and NL63) and Middle East Respiratory Syndrome Coronavirus. Subsequently, overlapped peptides in individual fragments (N1–N4) of NP were synthesized. N1-3 (25-GSNQNGERSGARSKQ-39), N3-1 (217-AALALLLLDRLNQL-230), and N4-8 (393-TLLPAADLDDFSKQL-407) were identified as major epitopes using enzyme-linked immunoassay (ELISA) and recognized by 47, 1, and 18 MAbs, respectively. The 24 remaining MAbs exhibited no reactivity with all synthetic peptides. Among MAb-epitope pairs, only MAbs targeting epitope N1-3 displayed no cross-reaction with NPs of SARS-CoV-1 and other SARS-related CoVs. All omicron variants contained a three-amino acid deletion (31ERS33) in the N1-3 region. Thus, MAbs targeting N1-3 failed to recognize these variants. Furthermore, a double-antibody sandwich ELISA for antigen detection was established using the optimal MAbs. Overall, a series of MAbs targeting SARS-CoV-2 NP was prepared, characterized with epitope mapping, and applied for the detection of SARS-CoV-2 antigens, and some novel B-cell epitopes of the viral NP were identified.

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Sacrococcygeal teratoma: Long‐term outcomes. A UK CCLG Surgeons Group Nationwide Study

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Abstract

Aim

Sacrococcygeal teratoma (SCT) is a rare paediatric germ cell tumour (1:40,000). Long-term data regarding urinary tract and bowel function after SCT resection is limited to few studies. A UK Children's Cancer and Leukaemia Group (CCLG) Surgeons multicentre study aimed to critically analyse long-term functional outcomes in patients following resection of SCT.

Methods

Nationwide study of UK paediatric surgical oncology centres using a standardised data collection form. All index cases of newborn infants and children <16 years with SCT diagnosis during 2005–2015 were included.

Results

165 SCT patients treated at 14 UK paediatric surgical oncology centres were included. Median age at presentation was 1 day [interquartile range, IQR: 0–25]; median age at surgery was 10 days [IQR: 4–150]. One hundred seventeen (70%) were female and 48 (30%) male. Antenatal diagnosis was made in 44% index cases. Total 59% of patients were Altman Stage I or II lesions. Follow-up data were available in 83% cases. Tumour recurrence occurred in 13 (7%) patients at median age 13 months [IQR: 8.75–30 months]. Fifty-nine (36%) of 165 patients had documented adverse bladder or bowel dysfunction. Twenty-two (37%) cases required urinary clean intermittent catheterisation (CIC) urology health care, with eight patients (14%) needing operative intervention to control management of bowel dysfunction.

Conclusion

This UK CCLG study showed 36% of SCT patients develop bladder or bowel dysfunction after primary tumour resection. Functional assessment of bladder and bowel function is mandatory during after-care follow-up of all SCT patients. A multidisciplinary care pathway, with surgeon speciality groups including surgical oncology, paediatric urology and paediatric colorectal specialists, is strongly advised to facilitate 'best practice' monitoring of long-term health and improve patient quality of life (QoL) into adulthood.

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InCISE: Instrument for Comprehensive Incisional and Surgical Evaluation

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InCISE: Instrument for Comprehensive Incisional and Surgical Evaluation

The evaluation of healing after head and neck surgery is currently qualitative and non-standardized. We developed InCISE: Instrument for comprehensive incisional and surgical evaluation to assess surgical wounds, which was found to be reliable, reproducible, and consistent.


Objective

The evaluation of healing after head and neck surgery is currently qualitative and non-standardized, limiting the quality of surgical healing assessments in clinical and research settings. We sought to develop an objective, standardized wound assessment score, and hypothesize that a reliable instrument can be developed to evaluate head and neck surgical wounds.

Methods

A prospective cohort study was conducted in a tertiary-care, academic head and neck surgery practice. Patients undergoing head and neck surgery were enrolled. A digital photograph protocol was developed for evaluating healing surgical wounds. A panel of experts developed and refined a wound healing score and established reliability, reproducibility, internal consistency, and validity of the score.

Results

InCISE: Instrument for comprehensive incisional and surgical evaluation was created. The utility of our wound healing score was assessed using classical test theory. We performed the major steps of establishing reliability in head and neck surgeons: (1) internal consistency (Cronbach's α = 0.81), (2) inter-observer reliability (intra-class correlation = 0.76), and (3) intra-rater reliability (intra-class correlation = 0.87), and content validity (through focus groups). Our composite measure was found to have strong internal consistency, inter-rater reliability, and intra-rater reliability. Preliminary work suggests criterion validity via associations with physical health related quality of life (SF-12).

Conclusion

A wound healing score for head and neck surgery, InCISE, has been developed and is reliable, reproducible, and consistent. Although content validity is present and criterion validity is suggested, work continues to establish validity in this instrument to allow for expanded clinical and research use.

Level of Evidence

N/A Laryngoscope, 2022

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USP36 promotes tumorigenesis and drug sensitivity of glioblastoma by deubiquitinating and stabilizing ALKBH5

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Abstract
Background
ALKBH5 is aberrantly activated and exerts critical roles in facilitating the development of glioblastoma. However, the underlying activation mechanism by which ALKBH5 protein is increased in glioblastoma is not completely understood. Our study aimed to elucidate the signaling pathways involved in mediating ALKBH5 protein stability.
Methods
The contribution of deubiquitinating enzymes (DUB) to the fluctuation of ALKBH5 protein expression were globally profiled with western blot analysis. Mass spectrometry and immunoprecipitation were performed to identify the USP36 and ALKBH5 interaction. The effects of USP36 on the stability of ALKBH5 were detected with in vivo and in vitro ubiquitination assays. Cell proliferation assays, neurosphere formation, limited dilution assay, and intracranial tumor growth assays were implemented to assess the co llaborative capacities of USP36 and ALKBH5 in tumorigenesis.
Results
Ubiquitin-specific peptidase 36 (USP36), as a potential ALKBH5-activating DUB, played an essential role in stabilization of ALKBH5 and regulation of ALKBH5 mediated gene expression in glioblastoma. The depletion of USP36 drastically impaired cell proliferation, deteriorated the self-renewal of GSCs and sensitized GSCs to temozolomide (TMZ) treatment. Furthermore, the deletion of USP36 substantially decreased the in vivo tumor growth when monitored by bioluminescence imaging. Our findings indicate that USP36 regulates the protein degradation and expression of ALKBH5, and the USP36-ALKBH5 axis orchestrates glioma tumorigenesis.
Conclusion
Our findings identify USP36 as a DUB of ALKBH5 and its role in glioblastoma progression, which may serve as a potential therapeutic target for glioblastoma treatment.
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Triple Antibiotic Paste Composition and use in Root Canal Treatment

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Triple Antibiotic Paste

Triple Antibiotic Paste is a type of Intra Canal Medicament which is used in Endodontic Treatment or Root canal Treatment to kill the micro organisms in the periapical region of an infected Root Canal. Triple antibiotic Paste or (TAP) consists of three medicines - Metronidazole, Ciprofloxacin and Minocycline. This combinati on of medicines have been found to be the best regimen to eliminate root canal pathogens. The most common microorganisms found in infected Root Canals are Peptostreptococcus spp, Actinomyces, Staphylococcus Salivarius, S. Sanguis, P. Endodontalis. The micro organisms most commonly infecting Failed or Re-infected root canals are "Enterococcus Faecalis". Triple Antibiotic paste uses: It is used as an Intracanal Medicament and in Regenerative Endodontics (Pulp Capping). It has been found to be very effective against E Feacalis which is a very stubborn bacteria found in Re-infected root canals. Composition of Triple antibiotic Paste: TAP is a combination of three antibiotics - Minocycline + Ciprofloxacin + Metronidazole. A combination of three antibiotics is required as any Infection of the Root Canal consists of multiple microorganisms of different types and to treat all these bacteria any single Antibiotic is sometimes not enough. A Combination of Antibiotics usually helps in treating the diverse flora of the Root Canal.
Triple Antibiotic Paste

How is Triple Antibiotics Paste prepared:

Hoshino et al. first proposed the combination of TPA and mentioned that the three Antibiotics - Metronidazole (500 mg) 30% + Minocycline (100mg) 30% + Ciprofloxacin (200mg) 30% + Propylene Glycol paste 10% should be mixed in a ratio of 1:1:1. These three components should have a carrier Glycol and macrogol ointment in a ratio of 1:1. The combination was later modified by making changes in the Ratios by Takushige et al. who proposed that the ratios should be Metronidazole + Minocycline + Ciprofloxacin - 3:3:1. A new Intra Canal Medicament known as MTAD was found to be useful in eliminating Enterococcus Faecalis strains  in a study published by Newberry et al. The MTAD is a combination of 3% Doxycycline, Citric Acid and a detergent polysorbate 80. MTAD should be used as an irrigation fluid inside the canals. MTAD should be used as the final irrigation rinse after using 1.3% Naocl and Saline. This has been found to remove the smear layer without altering the structure of dentinal tubules.
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Effects of calcium hydroxide intracanal medicament on push‐out bond strength of endodontic sealers: A systematic review and meta‐analysis

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Abstract

Objective

To investigate the effect of calcium hydroxide intracanal medicament on the push-out bond strength of resin-based and calcium silicate-based endodontic sealers.

Methods

A comprehensive search of was conducted for all relevant in-vitro studies. All randomized controlled in-vitro studies that evaluated the effect of calcium hydroxide on the push-out bond strength of resin-based or calcium silicate-based endodontic sealers were assessed. The variables of interest were extracted, and the risk of the included studies was evaluated. The standardized mean difference was calculated and the significance level was set at p value <0.05.

Results

A total of 26 studies were eligible for analysis. There were 45 independent comparison groups and 1009 recruited teeth. The pooled data showed no significant difference in push-out bond strength between calcium hydroxide and control group in the resin-based group (SMD = 0.03; 95% CI = −0.55, 0.60; p = 0.93), and calcium silicate-based group (SMD = 0.02; 95% CI = −0.31, 0.35; p = 0.90). Most of the studies (21 out of 26) were at medium risk of bias and five studies showed a low risk of bias.

Conclusion

The available evidence suggests that calcium hydroxide used as intracanal medication does not influence the push-out bond strength of the resin- and calcium silicate-based endodontic sealers.

Clinical significance

The results of this meta-analysis suggest that calcium hydroxide used as intracanal medication does not influence the push-out bond strength of resin-based and calcium silicate-based endodontic sealers.

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Maxillary vertical alveolar ridge augmentation using sandwich osteotomy technique with simultaneous versus delayed implant placement: A proof of principle randomized clinical trial

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Abstract

Background

The sandwich osteotomy technique usually requires high surgical skills and prolonged intraoperative time and had some technical drawbacks with a subsequent deficient amount of vertical bone gain. The aim of this study was to evaluate the final vertical bone gain using sandwich osteotomy with simultaneous versus delayed implant placement in the anterior maxilla.

Material and methods

This study included 16 patients having multiple missing maxillary anterior teeth with a vertically deficient alveolar ridge. Patients were randomly assigned into two equal groups. Both groups were treated using sandwich osteotomy with interpositional particulate bovine bone graft. In the study group (8 patients, 17 implants), the transport mobilized bone segment was fixed in position using simultaneous implant placement. Whereas in the control group (8 patients, 18 implants), micro-plates and screws were used, followed by a second-stage surgery for plates removal and delayed implant placement. Radiographic assessment included 4 months postoperative mean of vertical gain in alveolar ridge height, taken from cross-sectional cuts of cone beam CT.

Results

The mean vertical bone gain in the study group was 4.04 ± 0.59 mm compared to 3.86 ± 0.52 mm in the control group with no statistically significant difference (p = 0.518). The mean value of bone gain percentage in the study group was 33.02% compared to 31.75% in the control group, with no statistically significant difference (p = 0.656).

Conclusion

The sandwich osteotomy technique with simultaneous implant placement is a reliable method for vertical ridge augmentation that eliminates the need for a secondary surgery.

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Association between smoking and Schneiderian membrane perforation during maxillary sinus floor augmentation: A systematic review and meta‐analysis

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Abstract

Objective

To estimate the association between smoking and Schneiderian membrane perforation in sinus floor augmentation.

Materials and methods

Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Data were extracted by two authors independently. The inclusion criteria were the (1) age of patients >18, (2) the number of participants >10, and (3) smoking and the patients of Schneiderian membrane perforation were accurately recorded. The risk of bias was assessed by the Newcastle–Ottawa scale (NOS). Statistics analyses were conducted using Reman5.4.1 and Stata (15.0). The association of Schneiderian membrane perforation with smoking habits during maxillary sinus floor elevation was expressed as odds ratios (ORs) with a 95% confidence interval (95% CIs). And the I 2 statistic was used to estimate statistical heterogeneity. The funnel plot and Egger's tests were used to evaluate the reliability and stability of the results.

Results

Of 1463 articles screened, nine studies were included in our systematic review, and eight were synthesized for meta-analysis. Eight were retrospective observational studies and one was a clinical trial, with a total of 1424 patients included. The nine studies were proved as high quality according to the NOS. There was no significant publication bias in the studies (p = 0.827). A random-effects model was used because of differences in the adopted methodologies (p = 0.39, I 2 = 5%). During maxillary sinus augmentation, smoking and Schneiderian membrane perforation were associated (odds ratios, 1.58 [95% CI, 1.10–2.25]).

Conclusion

Smoking increased the risk of membrane perforation in maxillary sinus floor augmentation. Our evaluation was limited by the poor reporting of the number of cigarettes smoked per day (PROSPERO number was CRD42022306570).

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