Hypersensitivity in molar incisor hypomineralization: Superficial infiltration treatment

To date, there are no standardized protocols available in the literature for hypersensitivity treatment in molar incisor hypomineralization (MIH) patients. The aim of this study was to evaluate the efficacy of erosion\u2013infiltration treatments with resin in children with a strong hypersensitivity and also to develop a minimally invasive diagnostic\u2013therapeutic pathway for young MIH patients. Patients with clinical signs of MIH were enrolled according to international guidelines. A total of 42 patients (8\u201314 years old) with sensitivity of at least one molar and patients with post eruptive enamel fractures, but without dentin involvement or cavitated carious lesions were selected. A single superficial infiltration treatment with ICON (DMG, Germany) was performed with a modified etching technique. Sensitivity was tested with the Schiff Scale and Wong Baker Face Scale and was repeated at 12 months follow\u2010up. All patients reported lower sensitivity values at the end of the treatment. Significant differences of sensitivity according to the Schiff scale were reported between T0 and all subsequent follow\u2010ups, p < 0.05. The treatment of erosion infiltration with ICON resin is a minimally invasive preventive treatment that significantly improves the problem of hypersensitivity in permanent molars with MIH

Efficacy and safety of human papillomavirus vaccination in HIV-infected patients: a systematic review and meta-analysis

The prophylactic vaccines available to protect against infections by HPV are well tolerated and highly immunogenic. People with HIV have a higher risk of developing HPV infection and HPV-associated cancers due to a lower immune response, and due to viral interactions. We performed a systematic review of RCTs to assess HPV vaccines efficacy and safety on HIV-infected people compared to placebo or no intervention in terms of seroconversion, infections, neoplasms, adverse events, CD4+ T-cell count and HIV viral load. The vaccine-group showed a seroconversion rate close to 100% for each vaccine and a significantly higher level of antibodies against HPV vaccine types, as compared to the placebo group (MD = 4333.3, 95% CI 2701.4; 5965.1 GMT EL.U./ml for HPV type 16 and MD = 1408.8, 95% CI 414.8; 2394.7 GMT EL.U./ml for HPV type 18). There were also no differences in terms of severe adverse events (RR = 0.6, 95% CI 0.2; 1.6) and no severe adverse events (RR = 0.6, 95% CI 0.9; 1.2) between vaccine and placebo groups. Secondary outcomes, such as CD4 + T-cell count and HIV viral load, did not differ between groups (MD = 14.8, 95% CI − 35.1; 64.6 cells/µl and MD = 0.0, 95% CI − 0.3; 0.3 log10 RNA copies/ml, respectively). Information on the remaining outcomes was scarce and that did not allow us to combine the data. The results support the use of the HPV vaccine in HIV-infected patients and highlight the need of further RCTs assessing the effectiveness of the HPV vaccine on infections and neoplasms

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study.

Purpose Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL). Experimental design This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis. Results Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25). Conclusion No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages

Breathlessness, but not cough, suggests chronic obstructive pulmonary disease in elderly smokers with stable heart failure.

Chronic obstructive pulmonary disease (COPD) is a common comorbidity of heart failure (HF), but remains often undiagnosed, and we aimed to identify symptoms predicting COPD in HF. As part of an observational, prospective study, we investigated stable smokers with a confirmed diagnosis of HF, using the 8-item COPD-Assessment-Test (CAT) questionnaire to assess symptoms. All the items were correlated with the presence of COPD, and logistic regression models were used to identify independent predictors. 96 HF patients were included, aged 74, 33% with COPD. Patients with HF and COPD were more symptomatic, but only breathlessness when walking up a hill was an independent predictor of COPD (odds ratio=1.33, p=0.0484). Interestingly, COPD-specific symptoms such as cough and phlegm were not significant. Thus, in elderly smokers with stable HF, significant breathlessness when walking up a hill is most indicative of associated COPD, and may indicate the need for further lung function evaluation

Photobiomodulation of human fibroblasts and keratinocytes with blue light: Implications in wound healing

In recent years, photobiomodulation (PBM) has been recognized as a physical therapy in wound management. Despite several published research papers, the mechanism underlying photobiomodulation is still not completely understood. The investigation about application of blue light to improve wound healing is a relatively new research area. Tests in selected patients evidenced a stimulation of the healing process in superficial and chronic wounds treated with a blue LED light emitting at 420 nm; a study in animal model pointed out a faster healing process in superficial wound, with an important role of fibroblasts and myofibroblasts. Here, we present a study aiming at evidencing the effects of blue light on the proliferation and metabolism in fibroblasts from healthy skin and keratinocytes. Different light doses (3.43, 6.87, 13.7, 20.6, 30.9 and 41.2 J/cm2) were used to treat the cells, evidencing inhibitory and stimulatory effects following a biphasic dose behavior. Electrophysiology was used to investigate the effects on membrane currents: healthy fibroblasts and keratinocytes showed no significant differences between treated and not treated cells. Raman spectroscopy revealed the mitochondrial Cytochrome C (Cyt C) oxidase dependence on blue light irradiation: a significant decrease in peak intensity of healthy fibroblast was evidenced, while it is less pronounced in keratinocytes. In conclusion, we observed that the blue LED light can be used to modulate metabolism and proliferation of human fibroblasts, and the effects in wound healing are particularly evident when studying the fibroblasts and keratinocytes co-cultures

Anti-GD2 CAR MSCs against metastatic Ewing's sarcoma

Background: Ewing's sarcoma (ES) is an aggressive cancer affecting children and young adults. We pre-clinically demonstrated that mesenchymal stromal/stem cells (MSCs) can deliver tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) against primary ES after local injection. However, ES is often metastatic calling for approaches able to support MSC targeting to the ES multiple remote sites. Considering that the disialoganglioside GD2 is expressed by ES and to optimise MSC tumour affinity, bi-functional (BF) MSCs expressing both TRAIL and a truncated anti-GD2 chimeric antigen receptor (GD2 tCAR) were generated and challenged against ES. Methods: The anti-GD2 BF MSCs delivering a soluble variant of TRAIL (sTRAIL) were tested in several in vitro ES models. Tumour targeting and killing by BF MSCs was further investigated by a novel immunodeficient ES metastatic model characterized by different metastatic sites, including lungs, liver and bone, mimicking the deadly clinical scenario. Findings: In vitro data revealed both tumour affinity and killing of BF MSCs. In vivo, GD2 tCAR molecule ameliorated the tumour targeting and persistence of BF MSCs counteracting ES in lungs but not in liver. Interpretation: We here generated data on the potential effects of BF MSCs within a complex ES metastatic in vivo model, exploring also the biodistribution of MSCs. Our BF MSC-based strategy promises to pave the way for potential improvements in the therapeutic delivery of TRAIL for the treatment of metastatic ES and other deadly GD2-positive malignancies

Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial

Background: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer.Patients and methods: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (a = 0.05, power = 0.80). The proposed treatment could be considered promising if >= 13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365).Results: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation).Conclusion: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation

Early palliative care versus usual haematological care in multiple myeloma: retrospective cohort study

Objectives Although early palliative care (EPC) is beneficial in acute myeloid leukaemia, little is known about EPC value in multiple myeloma (MM). We compared quality indicators for palliative and end of life (EOL) care in patients with MM receiving EPC with those of patients who received usual haematological care (UHC).Methods This observational, retrospective study was based on 290 consecutive patients with MM. The following indicators were abstracted: providing psychological support, assessing/managing pain, discussing goals of care, promoting advance care plan, accessing home care services; no anti MM treatment within 14 and 30 days and hospice length of stay >7 days before death; no cardiopulmonary resuscitation, no intubation, <2 hospitalisations and emergency department visits within 30 days before death. Comparisons were performed using unadjusted and confounder adjusted regression models.Results 55 patients received EPC and 231 UHC. Compared with UHC patients, EPC patients had a significantly higher number of quality indicators of care (mean 2.62 +/- 1.25 vs 1.12 +/- 0.95; p<0.0001)); a significant reduction of pain intensity over time (p<0.01) and a trend towards reduced aggressiveness at EOL, with the same survival (5.3 vs 5.46 years; p=0.74)).Conclusions Our data support the value of integrating EPC into MM routine practice and lay the groundwork for future prospective comparative studies

Programmable Assembly of DNA-Functionalized Liposomes by DNA

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/nn1030093Bionanotechnology involves the use of biomolecules to control both the structure and property of nanomaterials. One of the most studied examples is DNA-directed assembly of inorganic nanoparticles such as gold nanoparticles (AuNPs). However, systematic studies on DNA-linked soft nanoparticles, such as liposomes, are still lacking. We herein report the programmable assembly and systematic characterization of DNA-linked liposomes as a function of liposome size, charge, fluidity, composition, DNA spacer, linker DNA sequence, and salt concentration for direct comparison to DNA-directed assembly of AuNPs. Similar to the assemblies of AuNPs, sharp melting transitions were observed for liposomes where the first derivative of the melting curve full width at half-maximum (fwhm) is equal to or less than 1 °C for all of the tested liposomes, allowing sequence specific DNA detection. We found that parameters such as liposome size, charge, and fluidity have little effect on the DNA melting temperature. Cryo-TEM studies showed that programmable assemblies can be obtained and that the majority of the liposomes maintained a spherical shape in the assembled state. While liposome and AuNP systems are similar in many aspects, there are also important differences that can be explained by their respective physical properties.University of Waterloo || Natural Sciences and Engineering Research Council |