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The study evaluated the antibacterial and anti-inflammatory efficacy, domiciliary oral hygiene, of a mouthrinse containing Tea Tree Oil (TTO) comparing it with two mouthrinses containing chlorhexidine 0,12% respectively and essential oils and a placebo. Materials and methods. A pilot study, randomized 4 × 4, controlled, cross-over, double-blind. 16 subjects with gingivitis (7 males and 9 females) aged 21-37 years, were randomly divided into four groups based on mouthwash that had to be used for domiciliary oral hygiene: mouthwash with essential oils, mouthwash with chlorhexidine 0,12 %, mouthwash containig tea tree oil and mouthwash placebo. Clinical evaluation was performed by: Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), Gingival Index (GI), discolorations, language examination and alteration of taste. The data were recorded before and 2 weeks after treatment. Results. Statistical analysis shows that treatments with tea tree oil, essential oils and chlorhexidine are effective. Comparing treatments should be noted that the tea tree oil gives a greater improvement in the GI and FMBS, while it is the least effective in the control of bacterial plaque. Conclusion. Although further studies are needed, the anti-inflammatory properties of the mouthwash made from TTO would seem to be a valuable non-toxic adjunct in the management of gingivitis. [ABSTRACT FROM AUTHOR]

Object. The aim of this paper is to present a clinical case in which the CAD-CAM procedure was applied for a prosthetic rehabilitation on implants. Materials. Digital CAD-CAM production by laboratory of the final restoration. Results. CAD-CAM production offers the opportunity to easily collaborate with laboratory. This prosthetic production gives better and demonstrated clinical results for the patient. Conclusion. CAD-CAM production is a very important instrument for prosthetic team. This work-flow compared with traditional methods is faster, precise and predictable. [ABSTRACT FROM AUTHOR]

Background: We evaluated shedding of epidermal growth factor type II receptor (Her2/neu) extracellular domain (ECD) in primary uterine serous carcinoma (USC) cell lines and in the serum of USC patients and its biological effects in experiments of trastuzumab-induced cytotoxicity in vitro.Methods: Her2/neu expression was evaluated by immunohistochemistry (IHC), real-time PCR and flow cytometry, while c-erbB2 gene amplification was assessed using fluorescent in situ hybridisation (FISH). Her2/neu ECD levels in the supernatants of USC cell lines and in the serum of 38 USC patients and 19 controls were tested using ELISA. The biologic effect of Her2/neu ECD on trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated in 5-h chromium-release assays.Results: Five out of ten USC cell lines overexpressed Her2/neu by IHC and showed amplification of the c-erbB2 gene. High levels of Her2/neu ECD were found in supernatants of all FISH-positive tumours. In contrast, FISH-negative USC was negative for Her2/neu ECD shedding. Serum Her2/neu ECD levels in patients harbouring 3+Her2/neu tumours were higher than those found in healthy women (P=0.02) or USC patients with 2+ or 1+/negative Her2/neu expression (P=0.02). In cytotoxicity experiments, trastuzumab-mediated ADCC was significantly decreased by the addition of Her2/neu ECD-containing supernatants (P=0.01).Conclusion: FISH-positive c-erbB2 USC cell lines shed high levels of Her2/neu ECD. High levels of Her2/neu ECD in USC patients may reduce trastuzumab-mediated ADCC in vitro and potentially neutralise its therapeutic effect in vivo. [ABSTRACT FROM AUTHOR]

Abstract: The lysozyme of hen''s egg white is used in winemaking to control spontaneous lactic acid bacteria (LAB). A total of eight LAB strains, isolated from grape must and wine, were used to assess the inhibitory effects of wine phenolics on lysozyme activity. The presence of phenolics, extracted from grape pomace, in growth medium reduced the mortality rate due to the lysozyme activity. This effect was especially clear in the case of strains belonging to Lactobacillus uvarum, Pediococcus parvulus and Oenococccus oeni, which are more sensitive to lysozyme than L. plantarum and L. hilgardii strains. Cell lysis assays carried out on four strains sensitive to lysozyme and Micrococcus lysodeikticus ATCC 4698, used as a reference strain, confirmed the inhibition of grape pomace phenolics on the muramidase. There was no interference from non-flavonoids, flavanols and flavonol compounds, when they were tested individually, on the lysozyme activity against the strains. Anthocyanins extracted from grape skins slightly inhibited the activity only against M. lysodeikticus. However, proanthocyanidins extracted from seed berries, strongly inhibited the lysozyme. In this extract, dimers were the predominant oligomers of flavan-3-ol. The study demonstrated that the effectiveness of lysozyme against LAB in red winemaking is related to the amount of low molecular weight proanthocyanidins that are released when the grapes are macerating. [Copyright &y& Elsevier]

Abstract Background We evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines. Materials and methods Trop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells. Results Trop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2. Conclusion Trop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2.

The garden strawberry (Fragaria x ananassa Duch.) is cultivated and consumed worldwide because of the pleasant flavor and health-promoting phytochemicals of its false fruits. Monocrop cultivars produce fully ripe strawberries in about one month post-anthesis throughout the spring, while everbearing cultivars undergo additional strawberry production in autumn. In this work, we evaluated the impact of different season-dependent environmental conditions on the ripening program of an everbearing field-gown strawberry variety from autumn 2015 to spring 2016. We combined ad hoc sampling and environmental data collection with LC-MS-based untargeted metabolomics to dissect the effects of cumulative temperature and solar irradiation on fruit quality parameters and secondary metabolism during ripening. Different dynamics in specific sub-groups of metabolites were observed in strawberries experiencing distinct amounts of cumulative temperature and solar irradiation during spring and autumn. The integration of statistical analyses on collected data revealed that solar irradiation mainly affected fruit fresh weight and organic acid levels, whereas temperature had a more selective effect on the accumulation of specific flavonols, anthocyanins, and soluble sugar. These findings are of suitable interest to design further approaches for the study of the complex interactions among environmental conditions and ripening in strawberries grown in a real-world scenario., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The incidence of neurodegenerative disorders like Alzheimer's or Parkinson's Disease, characterized by a progressive cognitive decline, is rising worldwide. Despite the considerable efforts to unveil the neuropsychological bases of these diseases, there is still an unmet medical need for effective therapies against cognitive deficits. In recent years, increasing laboratory evidence indicates the potential of phytotherapy as an integrative aid to improve cognitive functions. In this review, we describe the data of plant whole extracts or single compounds' efficacy on validated preclinical models and neuropsychological tests, aiming to correlate brain mechanisms underlying rodent behavioral responses to human findings. After a search of the literature, the overview was limited to the following plants: Dioscorea batatas , Ginkgo biloba , Melissa officinalis , Nigella sativa , Olea europaea , Panax ginseng , Punica granatum , and Vitis vinifera . Results showed significant improvements in different cognitive functions, such as learning and memory or visuospatial abilities, in both humans and rodents. However, despite promising laboratory evidence, clinical translation has been dampened by a limited pharmacological characterization of the single bioactive components of the herbal products. Depicting the contribution of the single phytochemicals to the phytocomplex's pharmacological efficacy could enable the comprehension of their potential synergistic activity, leading to phytotherapy inclusion in the existing therapeutic package against cognitive decline., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

The genus Agave comprises over 400 species that are known for their diverse applications, which include being sources of fiber, food, and beverages. There has recently been increased interest in exploring the metabolic content of this genus, and in this respect, saponins are the main compounds of interest. Saponins for Agave bracteosa have not been described to date, and the current work addresses the dereplication of a saponin-rich fraction to identify the structures of six compounds. The dereplication methods involve the use of UPLC-MS E analysis, NMR spectroscopy and published data for Agave saponins. A green extraction and isolation provided ten pure saponins. Remarkably, nine of these saponins have not been reported previously, namely (25 S )-cantalasaponin-1 and bractofuranosides A-H. These compounds were tested for cytotoxic activity. Bractofuranosides B ( 5 ) and G ( 10 ) displayed 57% and 53% cell viability on HeLa cells at 100 µM, respectively.

Background: Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi)., Materials and Methods: This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov., Results: The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients., Conclusions: PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.

The efficacy of hyaluronic acid instillations as therapy for patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) has been demonstrated in some clinical studies, with response rates up to 70%. The aim of the study is to investigate the change in symptoms and quality of life in female patients with IC/BPS after intravesical instillations of hyaluronic acid used as first-line treatment. A retrospective single-center cohort study was conducted. Female patients, whose symptoms were compatible with the diagnosis of IC/BPS as defined by the International Continence Society, were treated with a variable number of intravesical instillations of a hyaluronic acid-based drug. Three validated questionnaires were administered by telephone to all patients, before the beginning of the treatment and 6 months after the last administration of the drug. A total of 50 patients with symptoms compatible with the diagnosis of IC/BPS were included in the study. The median number of instillations performed is 4. For all questionnaires, the median value was significantly reduced following treatment with intravesical instillations ( p = 0.000). The present study has shown that intravesical hyaluronic acid treatment results in both statistically and clinically significant symptomatic improvement, thereby improving the quality of life of patients with IC/BPS.

Species from genus Artemisia are widely distributed throughout temperate regions of the northern hemisphere and many cultures have a long-standing traditional use of these plants as herbal remedies, liquors, cosmetics, spices, etc. Nowadays, the discovery of new plant-derived products to be used as food supplements or drugs has been pushed by the exploitation of bioprospection approaches. Often driven by the knowledge derived from the ethnobotanical use of plants, bioprospection explores the existing biodiversity through integration of modern omics techniques with targeted bioactivity assays. In this work we set up a bioprospection plan to investigate the phytochemical diversity and the potential bioactivity of five Artemisia species with recognized ethnobotanical tradition (A. absinthium, A. alba, A. annua, A. verlotiorum and A. vulgaris), growing wild in the natural areas of the Verona province. We characterized the specialized metabolomes of the species (including sesquiterpenoids from the artemisinin biosynthesis pathway) through an LC-MS based untargeted approach and, in order to identify potential bioactive metabolites, we correlated their composition with the in vitro antioxidant activity. We propose as potential bioactive compounds several isomers of caffeoyl and feruloyl quinic acid esters (e.g. dicaffeoylquinic acids, feruloylquinic acids and caffeoylferuloylquinic acids), which strongly characterize the most antioxidant species A. verlotiorum and A. annua. Morevoer, in this study we report for the first time the occurrence of sesquiterpenoids from the artemisinin biosynthesis pathway in the species A. alba., (© 2024. The Author(s).)

Background: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV)., Methods: Patients with COVID-19 pneumonia admitted up to May 28 th , 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan., Results: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes., Conclusions: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Background: COVID-19 acute respiratory distress syndrome (ARDS) is often managed with mechanical ventilation (MV), requiring sedation and paralysis, with associated risk of complications. There is limited evidence on the use of high flow nasal cannula (HFNC). We hypothesized that management of COVID-19 ARDS without MV is feasible., Methods: Included were all adult patients diagnosed with COVID-19 ARDS, with PaO2/FiO2 ratio <100 at admission, and whose management was initially performed without MV. We evaluated need for intubation during ICU stay, mortality and hospital/ICU length of stay (LOS)., Results: Out of 118 patients, 41 were managed only with HFNC from hospital admission (and at least during first 24 hours in ICU) and had a PaO2/FiO2 ratio <100 (72.9±13.0). Twenty-nine out of 41 patients never required MV: 24 of them survived and were discharged home. Their median ICU LOS was 11 (7-17) days, and their hospital LOS was 29 (18-45) days. We identified PaO2/FiO2 ratio at ICU admission as the only significant predictor for need for MV during ICU stay. We also identified age, length of non-invasive respiratory support before ICU admission, mean value of PaO2/FiO2 ratio during first half and whole ICU stay as predictors of mortality., Conclusions: It is safe to monitor in ICU and use HFNC in patients affected by COVID-19 ARDS who initially present data suggesting an early need for intubation. The 41 patients admitted with a PaO2/FiO2 ratio <100 and initially treated only with HFNC show a 22% mortality that is in the lower range of what is reported in recent literature.

Objective: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. Design: Prospective observational study. Setting: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. Participants: Adult patients receiving mechanical ventilation due to COVID-19. Interventions: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. Main outcome measures: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. Results: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87-16.22; P = 0.013) and the PaO 2 /FiO 2 ratio (median difference, 23.17; 95% CI, 3.46-42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09-0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). Conclusions: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and PaO 2 /FiO 2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. Trial registration: ClinicalTrials.gov NCT04318366., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Purpose: Uterine myomas are the most common gynecological disease. In these cases, a myomectomy is performed traditionally laparotomically. However, alternatives have been widely used, including laparoscopic, endoscopic, and robotic surgery. During these techniques, diffuse parenchymatous bleeding remains one of the main intraoperative and postoperative complications and sometimes requires unplanned hysterectomies. Recently, hemostatic agents and sealants have been used to prevent excessive blood loss during surgical repair., Methods: We propose a prospective case-control study on the use of a sealing hemostat patch (HEMOPATCH ® ) on uterine sutures in laparotomic myomectomy. In the period between July 2016 and April 2017, 46 patients with symptomatic uterine fibromatosis underwent surgery. They were divided into two groups of 23 patients, with different treatments in the hemostatic phase of oozing bleeding. HEMOPATCH ® is applied in group A, and spray electrocoagulation is applied in group B., Results: In group A, we achieve faster hemostasis (p < 0.05), than in group B. We report a significantly lower C-reactive protein value on the second and third days after surgery for group A compared to group B., Conclusions: HEMOPATCH ® , during laparotomic myomectomy, is a valid alternative solution for obtaining rapid hemostasis and consequently intraoperative and postoperative bleeding. Furthermore, we suggest that a lower inflammatory peritoneal state is probably correlated with the barrier effect of the patch on the suture., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A promising alternative to comprehensively performing genomics experiments is to, instead, perform a subset of experiments and use computational methods to impute the remainder. However, identifying the best imputation methods and what measures meaningfully evaluate performance are open questions. We address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. We find that imputation evaluations are challenging and confounded by distributional shifts from differences in data collection and processing over time, the amount of available data, and redundancy among performance measures. Our analyses suggest simple steps for overcoming these issues and promising directions for more robust research., (© 2023. The Author(s).)

Species of Myrtaceae Juss., the ninth largest family of flowering plants, are a valuable source of bioactive specialized metabolites. A leading position belongs to phloroglucinol derivatives, thanks to their unusual structural features and biological and pharmacological properties. Myrcianthes cisplatensis (Cambess.) O. Berg, a common tree on the banks of rivers and streams of Uruguay, southern Brazil, and northern Argentina, with aromatic leaves, is known as a diuretic, febrifuge, tonic, and good remedy for lung and bronchial diseases. Despite knowledge about traditional use, few data on its phytochemical properties have been reported in the literature. The methanol extract of M. cisplatensis , grown in Arizona, USA, was first partitioned between dichloromethane and water and then with ethyl acetate. The enriched fractions were evaluated using a broth microdilution assay against Staphylococcus aureus ATCC 29213 and 43300 (methicillin-resistant S. aureus (MRSA)). The potential antimicrobial activity seemed to increase in the dichloromethane extract, with a MIC value of 16 µg/mL against both strains. Following a bio-guided approach, chromatographic techniques allowed for isolating three coumarin derivatives, namely endoperoxide G3, catechin, and quercitrin, and four new p -coumaroyl alkylphloroglucinol glucosides, named p -coumaroylmyrciacommulone A-D. Their structures were characterized through spectroscopic techniques: 2D-NMR experiments (HSQC, HMBC, and HSQC-TOCSY) and spectrometric analyses (HR-MS). The antimicrobial assessment of pure compounds against S. aureus ATCC 29213 and ATCC 43300 demonstrated the best activity for p -coumaroylmyrciacommulone C and D with the growth inhibition of 50% at 32 µg/mL against both strains of S. aureus .

Plants are valuable sources of secondary metabolites with pharmaceutical properties, but only a small proportion of plant life has been actively exploited for medicinal purposes to date. Underexplored plant species are therefore likely to contain novel bioactive compounds. In this study, we investigated the content of secondary metabolites in the flowers, leaves and pseudobulbs of the orchid Oncidium sotoanum using an untargeted metabolomics approach. We observed the strong accumulation of C-diglycosylated chrysin derivatives, which are rarely found in nature. Further characterization revealed evidence of antioxidant activity (FRAP and DPPH assays) and potential activity against neurodegenerative disorders (MAO-B inhibition assay) depending on the specific molecular structure of the metabolites. Natural product bioprospecting in underexplored plant species based on untargeted metabolomics can therefore help to identify novel chemical structures with diverse pharmaceutical properties.