WIMPs search by scintillators: possible strategy for annual modulation search with large-mass highly-radiopure NaI(Tl)

The DAMA experiments are running deep underground in the Gran Sasso National Laboratory. Several interesting results have been achieved so far. Here a maximum likelihood method to search for the WIMP annual modulation signature is discussed and applied to a set of preliminary test data collected with large mass highly radiopure NaI(Tl) detectors. Various related technical arguments are briefly addressed.Comment: 6 pages, 4 figures, LaTex. Contributed paper to TAUP97; to appear in the Proceeding

Ultra-Low Frequency TENS as an Adjunctive Therapy for Pain Management in Non-Surgical Periodontal Treatment: A Pilot Study

Introduction: non-surgical periodontal treatment, primarily comprising scaling and root planing, is crucial for the maintenance and enhancement of oral health. However, the invasive nature of this procedure often leads to patient discomfort and pain, which may deter individuals from seeking necessary dental care, ultimately compromising their oral health outcomes. Methods: This prospective randomized crossover split-mouth study involved the application of Ultra-Low Frequency (ULF) Transcutaneous Electrical Nerve Stimulation (TENS) in 20 adult patients undergoing non-surgical periodontal treatment. Pain and discomfort levels were quantitatively assessed during procedures conducted with and without the ULF-TENS intervention. Results: The assessment of maximum voluntary opening, pain intensity, and overall comfort levels indicated a statistically significant reduction in pain (p < 0.0001) and discomfort (p < 0.0001) when ULF-TENS was employed during the treatment, and an increase in the maximum mouth opening after TENS (p = 0.00062). Conclusions: The findings of this pilot study suggest that ULF-TENS may serve as a valuable adjunctive therapy in non-surgical periodontal treatment by reducing pain and discomfort, potentially enhancing patient comfort and compliance. Further research with larger sample sizes is warranted to confirm these findings

Effects of trigeminal neurostimulation on heart rate variability: comparing cutaneous (Tragus) and tongue (Antero-Dorsal mucosa) stimulation

BackgroundTrigeminal neurostimulation of the dorsal anterior mucosal surface of the tongue has been proposed to treat a variety of pathologies and to promote neuro-muscular coordination and rehabilitation. Dental ULFTENS can also be considered a form of trigeminal neurostimulation applied to the skin surface bilaterally at the level of the tragus. It has been used for years in dentistry for practical and diagnostic purposes. Previous work has combined the two stimulation techniques showing an efficacy in improving HRV in healthy young women of dental ULFTENS applied to the mucosal surface of the tongue. This work sought to assess whether there is a difference in HRV in relation to the site of application of dental ULFTENS (tragus vs. tongue). If effective in reducing the activity of arousal circuits, this tongue-level stimulation technique could have new clinical applications.Material and methodA new intraoral device allowed electrical stimulation of the dorsal anterior mucosa of the tongue in 80 healthy young women divided into two groups: TUD group (ULFTENS stimulation on the mucosa of the tongue) and Tragus group (stimulation with ULFTENS bilaterally in the area of the tragus). The effects on HRV were monitored by photoplethysmographic wave (PPG). The HRV parameters studied were RMSSD, HF, LF, LF/HF.ResultsOnly the TUD group showed a significant change in selected HRV parameters that was maintained even in the epoch after the end of electrical stimulation. This effect can be considered as a vagal activation and an increased of HRV parameter. The Tragus group did not show significant change in the direction of increased HRV but showed an opposite trend. There were no undesirable or annoying effects of stimulation.ConclusionStimulation of the dorsal anterior (trigeminal) mucosal surface of the tongue with ULFTENS applied with an intraoral device was shown to be able to increase HRV while the same stimulation on tragus area, according to traditional dental ULFTENS procedure, did not show the same effects.Clinical implicationsThis stimulation technique could be an aid in the diagnosis and treatment of disorders characterized by autonomic disequilibrium such as, in the dental field, TMDs.Trial registration"Effects of Trigeminal Neurostimulation on Heart Rate Variability: Comparing Tragus and Tongue Stimulation". ID number: NCT06549205. Date of first registration: August 1st 2024. https://clinicaltrials.gov/study/NCT06549205?id= NCT06549205&rank=1

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Trigeminal electrical stimulation with ULFTENS of the dorsal anterior mucosal surface of the tongue: Effects on Heart Rate Variability (HRV)

Background: Trigeminal electrical stimulation of the dorsal anterior mucosal surface of the tongue has demonstrated its efficacy in a variety of neurological disorders in which anatomical or functional alterations are present. The pathogenesis of such disorders is often linked to altered arousal circuits, and the benefits of tongue stimulation are attributed to the rebalancing of this system. Dental ULFTENS shows efficacy in acting on the muscular, autonomic system and control of the descending pathways that modulate pain. It is administered at the skin level in the area anterior to the tragus and not on the mucosal surface of the tongue. The use of this stimulation technique at the tongue level could have new applications and clinical results if it were able to reduce the activity of arousal circuits. Material and method: A new intraoral device allowed electrical stimulation of the dorsal anterior mucosa of the tongue in 32 healthy young women. The effects on HRV were monitored by photoplethysmographic wave (PPG) and compared with a control group. The HRV parameters studied were RMSSD, HF, LF, LF/HF, REC, DET. Results: The group of stimulated subjects showed a significant change in some of the HRV parameters that was maintained even in the epoch after the end of electrical stimulation. This effect can be considered as a vagal activation and a change of HRV trend. The control group of unstimulated subjects showed an opposite trend. There were no undesirable or annoying effects of stimulation. Conclusion: Stimulation of the dorsal anterior (trigeminal) mucosal surface of the tongue with ULFTENS applied with an intraoral device was shown to be able to increase HRV

Evaluation of Physicochemical and Microbial Properties of Extracts from Wine Lees Waste of Matelica’s Verdicchio and Their Applications in Novel Cosmetic Products

Wine lees are sediments deposited on the walls and bottom of barrels resulting from wine fermentation and mainly consist of yeasts. Saccharomyces cerevisiae extracts, rich in beneficial components for the skin, have already been used in cosmesis, while wine lees have not been well exploited by the cosmetics industry yet. The aim of this work was the full characterization of the wine lees from Verdicchio's wine, with the aim to exploit it as a beneficial ingredient in new cosmetic products. After mapping the microbial composition of the sample waste, the parameters for the sonication extraction process were optimized and the physicochemical properties of the extract were analyzed. The efficiency of the aqueous extraction-and in particular the yeast cell lysis necessary for the release of proteins from the cell-was assessed by evaluating cell shape and size, and protein release, under scanning electron microscopy (SEM), dynamic light scattering (DLS) and Bradford's protein assays. Thus, the total phenol content and antioxidant capacity of the supernatant recovered from native and sonicated lees were determined by Folin-Ciocalteu's and spectrophotometric assays, respectively. To quantify the heavy metals and highlight the presence of microelements beneficial for the skin, inductively coupled plasma-mass spectrometry (ICP-MS) was applied. In vitro metabolic activity and cytotoxicity were tested on both HaCat keratinocytes and human gingival fibroblasts, showing that wine lees are safe for skin's cells. The results show that sonicated lees appear to be more interesting than native ones as a consequence of the release of the active ingredients from the cells. Due to the high antioxidant capacity, content of beneficial elements for skin and an appropriate microbiologic profile, wine lees were included in five new solid cosmetic products and tested for challenge test, compatibility with human skin, sensory analysis, trans epidermal water loss (TEWL) and sebometry

Temporal dynamics of early inflammatory markers after professional dental cleaning: a meta-analysis and spline-based meta-regression of TNF-α, IL-1β, IL-6, and (hs)CRP

Introduction: Chronic periodontitis is linked to systemic inflammation and cardiovascular risk, yet the temporal trajectory and magnitude of systemic cytokine reduction following nonsurgical-periodontal-therapy (NSPT) remain underexplored. We conducted a meta-analysis and spline-based meta-regression to assess whether intensive NSPT, compared to standard therapy, produces sustained reductions in circulating TNF-α, IL-1β, IL-6 and high-sensitivity C-reactive protein (hs-CRP). Methods: We systematically searched major databases for interventional studies published until January 2024 comparing intensive vs. standard NSPT on inflammatory markers. Using a custom R pipeline, standardized mean differences (SMDs), 95% confidence intervals (Cis) heterogeneity (I2) and stratified analyses by phenotype (e.g., smoking, diabetes) and time were performed. A spline-based mixed-effects meta-regression explored temporal dynamics of inflammatory reduction in the intensive group. Results: From 216 observations (14,374 paired values), intensive NSPT led to significantly greater reductions in TNF-α (SMD –0.59, 95% CI –1.02 to –0.16; P=0.008), IL-6 (SMD –0.20, 95% CI –0.39 to –0.00; P=0.046) and hs-CRP (SMD –1.17, 95% CI –2.18 to –0.16; P=0.024) compared to standard therapy. IL-1β showed a near-significant reduction (SMD –4.14, P=0.052). Standard therapy was paradoxically associated with greater CRP reduction (SMD –0.30, P=0.001). Age, tooth count and year of publication moderated effects. Early benefits emerged within 3 months for TNF-α and 6 months for IL-1β. Although no strong nonlinear time-response was confirmed (QM = 4.23, P=0.2372),a potential rebound in cytokine suppression was suggested. The overall anti-inflammatory effect remained significant. Discussion: Intensive NSPT reduces systemic inflammation particularly in younger, non-smoking individuals. The potential rebound in inflammatory markers underscores the need for longitudinal studies but, supports the systemic immunoregulatory effect of periodontal therapy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CDR42024503063

Small nucleolar RNAs determine resistance to doxorubicin in human osteosarcoma

Doxorubicin (Dox) is one of the most important first-line drugs used in osteosarcoma therapy. Multiple and not fully clarified mechanisms, however, determine resistance to Dox. With the aim of identifying new markers associated with Dox-resistance, we found a global up-regulation of small nucleolar RNAs (snoRNAs) in human Dox-resistant osteosarcoma cells. We investigated if and how snoRNAs are linked to resistance. After RT-PCR validation of snoRNAs up-regulated in osteosarcoma cells with different degrees of resistance to Dox, we overexpressed them in Dox-sensitive cells. We then evaluated Dox cytotoxicity and changes in genes relevant for osteosarcoma pathogenesis by PCR arrays. SNORD3A, SNORA13 and SNORA28 reduced Dox-cytotoxicity when over-expressed in Dox-sensitive cells. In these cells, GADD45A and MYC were up-regulated, TOP2A was down-regulated. The same profile was detected in cells with acquired resistance to Dox. GADD45A/MYC-silencing and TOP2A-over-expression counteracted the resistance to Dox induced by snoRNAs. We reported for the first time that snoRNAs induce resistance to Dox in human osteosarcoma, by modulating the expression of genes involved in DNA damaging sensing, DNA repair, ribosome biogenesis, and proliferation. Targeting snoRNAs or down-stream genes may open new treatment perspectives in chemoresistant osteosarcomas

Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines

Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al