Exploring the urban arbovirus landscape in Rio de Janeiro, Brazil: transmission dynamics and patterns of disease spread.

Background: This study focuses on urban arboviruses, specifically dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV), which pose a significant public health challenge in Rio de Janeiro state, Southeast Brazil. In our research, we highlight critical findings on the transmission dynamics of these arboviruses in Rio de Janeiro, identifying distinct patterns of disease spread. Methods: By combining genomic data with case reports from the Brazilian Ministry of Health, we have analysed the phylogenetics, prevalence and spatial distribution of these endemic viruses within the state. Findings: Our results revealed sustained DENV transmission primarily in the northern part of the state, a significant ZIKV epidemic in 2016 affecting all mesoregions, and two major CHIKV outbreaks in 2018 and 2019, predominantly impacting the northern and southern areas. Our analysis suggests an inverse relationship between arboviral case incidence and urban density, with less populous regions experiencing higher transmission rates, potentially attributed to a complex interplay of factors such as the efficacy of vector control measures, environmental conditions, local immunity levels, and human mobility. Furthermore, our investigation unveiled distinct age and gender trends among affected individuals. Notably, dengue cases were predominantly observed in young adults aged 32, while chikungunya cases were more prevalent among individuals over 41. In contrast, cases of ZIKV were concentrated around the 33-year age group. Intriguingly, females accounted for nearly 60% of the cases, suggesting a potential gender-based difference in infection rates. Interpretation: Our findings underscore the complexity of arbovirus transmission and the need for interventions tailored to different geographical mesoregions. Enhanced surveillance and genomic sequencing will be essential for a deeper, more nuanced understanding of regional arbovirus dynamics. Identifying potential blind spots within the state will be pivotal for developing and implementing more effective public health strategies, specifically designed to address the unique challenges posed by these viruses throughout the state. Funding: This study was supported by the National Institutes of Health USA grant U01 AI151698 for the United World Arbovirus Research Network (UWARN) and the CRP-ICGEB RESEARCH GRANT 2020 Project CRP/BRA20-03.

Fractional and Microablative CO2 LASER and Radiofrequency in the Treatment of Genitourinary Syndrome of Menopause: A Descriptive Study.

Objectives: This study aimed to evaluate the vagina clinically, cytologically, and histologically before and after treating genitourinary syndrome of menopause (GSM) with fractional microablative carbon dioxide LASER (CO2L), radiofrequency (RF), and estrogen vaginal cream (CT). Methods: Women with moderate-to-severe symptoms of GSM, denoted by a GSM Visual analog scale (VAS) score of >4, were eligible for this study. The patients were randomized into treatment groups. In the energy groups, three vulvovaginal applications were administered monthly. The CT group used 0.5 mg vaginal estriol cream for 14 consecutive days, followed by twice a week for 4 months. The follow-up visits occurred 120 days after the beginning of the treatments. The same parameters obtained at the first visit were re-evaluated: GSM VAS score, Incontinence Quality of Life Questionnaire (I-QOL), gynecological examination determining Vaginal Health Index (VHI), vaginal smear for Vaginal Maturation Value (VMV), and vaginal biopsy. Results: Seventy-one women were included, 48 completed the study and provided adequate samples for analysis (CO2L [21 patients], RF [15 patients], and CT [12 patients]). GSM symptoms, I-QOL, and VHI significantly improved after all proposed treatments, with no significant differences between them. VMV did not change after any treatment; however, only 22.9% of the patients presented with cytological atrophy before treatment. Histological vaginal atrophy was identified in 6 (12.5%) pretreated vaginal samples. After the intervention, all histological parameters were normalized, no tissue damage was observed, and no major clinical complications were observed. Conclusion: CO2L and RF seem to be good alternatives to CT for GSM treatment, with no tissue damage.

Creating a next-generation phenotype library: the health data research UK Phenotype Library.

Objective: To enable reproducible research at scale by creating a platform that enables health data users to find, access, curate, and re-use electronic health record phenotyping algorithms. Materials and Methods: We undertook a structured approach to identifying requirements for a phenotype algorithm platform by engaging with key stakeholders. User experience analysis was used to inform the design, which we implemented as a web application featuring a novel metadata standard for defining phenotyping algorithms, access via Application Programming Interface (API), support for computable data flows, and version control. The application has creation and editing functionality, enabling researchers to submit phenotypes directly. Results: We created and launched the Phenotype Library in October 2021. The platform currently hosts 1049 phenotype definitions defined against 40 health data sources and >200K terms across 16 medical ontologies. We present several case studies demonstrating its utility for supporting and enabling research: the library hosts curated phenotype collections for the BREATHE respiratory health research hub and the Adolescent Mental Health Data Platform, and it is supporting the development of an informatics tool to generate clinical evidence for clinical guideline development groups. Discussion: This platform makes an impact by being open to all health data users and accepting all appropriate content, as well as implementing key features that have not been widely available, including managing structured metadata, access via an API, and support for computable phenotypes. Conclusions: We have created the first openly available, programmatically accessible resource enabling the global health research community to store and manage phenotyping algorithms. Removing barriers to describing, sharing, and computing phenotypes will help unleash the potential benefit of health data for patients and the public.

Fibrosis-related transcriptome unveils a distinctive remodeling matrix pattern in penetrating ileal Crohn's disease.

BACKGROUND AND AIMS: Stricturing (B2) and penetrating (B3) ileal Crohn's disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn's disease. METHODS: Using Nanostring technology and comparative bioinformatics, we analyzed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture(s) (B3s) and 12 without (B3o). Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes a p-adjusted <0.05 and Fold Change ≤-1.5 or ≥ 1.5 was adopted. qPCR and immunohistochemistry analyses were used to validate selected differentially expressed genes. RESULTS: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn's disease localization, perianal disease and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn's disease fibrogenesis, while eight differentially expressed genes were so in other organs. The most significantly active biologic processes and pathways in penetrating disease were response to TGFßand matrix organization and degradation, as validated by immunohistochemistry. CONCLUSIONS: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn's disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodeling.

Health-related roles of older generations in families with inherited genetic conditions: a scoping review.

Inherited genetic conditions are family diseases. They affect consanguineous relatives, in lineage for several generations, and impact the family dynamics. Older generations have been considered highly influential in the health management of families with inherited genetic conditions. To our knowledge, no reviews so far addressed the health-related roles of older generations in these families. This scoping review aims to fill that gap by mapping the existent research about the health-roles roles performed by the older generations in families living with autosomal dominant inherited genetic conditions. Four electronic databases were searched: Scopus, Web of Science, PubMed, PsycInfo. Eleven studies were included, and relevant findings were extracted. Main roles included: informers vs. blockers of disease-related information; encouragers vs. discouragers of health screening or genetic testing; (non-)supporters; and role models in living and coping with the disease. The roles played by older generations are relevant to the health management of other family members and can be beneficial to themselves (reciprocal interactions). Acknowledging and understanding these roles is important for professionals and health-services. Results suggest the relevance of an intergenerational perspective when working with families with inherited genetic conditions.

Skin assessment in congenital untreated isolated GH deficiency.

PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype.

Importance: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. Objectives: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival. Design, Setting, and Participants: This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers. Main Outcomes and Measures: Accurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis. Results: Of 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03). Conclusions and Relevance: In this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

Influence of the Different Maturation Conditions of Cocoa Beans on the Chemical Profile of Craft Chocolates.

Cocoa beans (Theobroma cacao L.) can be used for craft chocolate production, which arouses consumer interest due to their perceived better quality. This study aimed to evaluate the chemical profile of 80% artisanal chocolate samples produced with cocoa beans subjected to different maturation conditions. In the first maturation process, beans were matured under no-oxygen conditions, and in the second, the toasted beans were matured in oak barrels. The volatile compounds of the chocolate samples were extracted by the solid-phase microextraction method in headspace mode and analyzed by gas chromatography/mass spectrometer. The non-volatile compounds were extracted with methanol and analyzed through paper spray mass spectrometry. Overall, 35 volatile compounds belonging to different chemical classes (acids, alcohols, aldehydes, ketones, esters, and pyrazines) were identified, such as propanoic acid and butane-2,3-diol. In addition, 37 non-volatile compounds, such as procyanidin A pentoside and soyasaponin B, were listed. Tannins, flavonoids, and phenylpropanoids were the main chemical classes observed, varying between the two samples analyzed. Therefore, it was possible to verify that maturation conditions affected the metabolomic profile of the 80% artisanal chocolate samples, being able to influence the sensory characteristics and bioactive compounds profile. Given these results, the sensory evaluation of these chocolates is suggested as the next step.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

DUSP3 modulates IRES-dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus.

BACKGROUND INFORMATION: The dual-specificity phosphatase 3 (DUSP3) regulates cell cycle progression, proliferation, senescence, and DNA repair pathways under genotoxic stress. This phosphatase interacts with HNRNPC protein suggesting an involvement in the regulation of HNRNPC-ribonucleoprotein complex stability. In this work, we investigate the impact of DUSP3 depletion on functions of HNRNPC aiming to suggest new roles for this enzyme. RESULTS: The DUSP3 knockdown results in the tyrosine hyperphosphorylation state of HNRNPC increasing its RNA binding ability. HNRNPC is present in the cytoplasm where it interacts with IRES trans-acting factors (ITAF) complex, which recruits the 40S ribosome on mRNA during protein synthesis, thus facilitating the translation of mRNAs containing IRES sequence in response to specific stimuli. In accordance with that, we found that DUSP3 is present in the 40S, monosomes and polysomes interacting with HNRNPC, just like other previously identified DUSP3 substrates/interacting partners such as PABP and NCL proteins. By downregulating DUSP3, Tyr-phosphorylated HNRNPC preferentially binds to IRES-containing mRNAs within ITAF complexes preferentially in synchronized or stressed cells, as evidenced by the higher levels of proteins such as c-MYC and XIAP, but not their mRNAs such as measured by qPCR. Under DUSP3 absence, this increased phosphorylated-HNRNPC/RNA interaction reduces HNRNPC-p53 binding in presence of RNAs releasing p53 for specialized cellular responses. Similarly, to HNRNPC, PABP physically interacts with DUSP3 in an RNA-dependent manner. CONCLUSIONS AND SIGNIFICANCE: Overall, DUSP3 can modulate cellular responses to genotoxic stimuli at the translational level by maintaining the stability of HNRNPC-ITAF complexes and regulating the intensity and specificity of RNA interactions with RRM-domain proteins.

HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

The Impact of Diabetes Education on Continuous Glucose Monitoring in SUS-Dependent Patients in a Northeastern Brazilian City.

BACKGROUND: Diabetes Mellitus (DM) is an important chronic disease that occurs worldwide. AIMS: This study aims to investigate how the use of the FreeStyle® Libre system in Unified Health System (SUS) patients impacts diabetes parameters in patients who receive education on proper insulin administration and the use of the continuous monitoring device, as well as how this affects patients without any concomitant multidisciplinary support in Sergipe, Brazil. METHODS: We conducted a prospective randomized study in a diabetes clinic in Sergipe, Brazil, using the flash method FreeStyle® Libre (Abbott). The participants were divided into two groups: one receiving diabetes education on CGM (continuous glucose monitoring), while the other did not. Before the intervention, the patient's treatment motivation and quality of life were assessed using a questionnaire, and baseline levels of glycated hemoglobin were measured using high-performance liquid chromatography (HPLC) and the point of care AlereTM Afinion with boronate fixation. We compared first- and second-phase data with respect to glycated hemoglobin, mean interstitial blood glucose, time on and above target for hypoglycemic and hyperglycemic events, and mean hypoglycemic duration. RESULTS: In group A, which received the diabetes education intervention, there was a significant reduction in average HbA1c levels from 8.6% to 7.9% after 3 months (p = 0.001). However, there was no significant difference in average glycemic values. Time above target decreased significantly from 50.62% to 29.43% (p = 0.0001), while time below target decreased from 22.90% to 20.21% (p = 0.002). There was no significant change in the number of hypoglycemic events, but the duration of hypoglycemia decreased significantly from 130.35 min to 121.18 min after 3 months (p = 0.0001). In Group B, there was no significant difference in mean HbA1c levels before (7.07%) and after (7.28%) sensor installation. This group maintained lower HbA1c levels compared to the other group. Average blood glucose levels also remained similar before (148.37 mg/dL) and after (154.65 mg/dL) the intervention. Although the time above the target glucose level increased significantly from 35.94% to 48.17%, the time at target decreased from 50.40% to 37.97%. No significant changes were observed in the time below target, the number of hypoglycemic events, or the duration of hypoglycemia. CONCLUSIONS: Our findings indicate that utilizing continuous glucose monitoring technology can enhance glycemic control, particularly in motivated, educated, low-income patients dependent on the SUS. To achieve positive results with FreeStyle Libre, it is imperative to allocate resources for multidisciplinary support.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Removal of phenolic compounds from sugarcane syrup and impact on Saccharomyces cerevisiae fermentation for ß-farnesene production.

This work aimed to study for the first time the effects of phenolic compounds from sugarcane syrup on Saccharomyces cerevisiae ß-farnesene fermentation by removing them from this feedstock. Syrup purification was optimized through a central composite design using five types of activated charcoal: three contact times (1-24 h) and three adsorbent concentrations (10-150 g L-1 ). The optimal purification condition-charcoal pellets at 115 g L-1 and contact time of 12.5 h-led to 96.7% of phenolic compounds removal and 43.7% of syrup recovery. The effects of reducing phenolic content from approximately 7.0-0.3 mg L-1 in sugarcane syrup on yeast fermentation varied with the scale. An increase in biomolecule productivity was only observed in shake-flasks (11%) and in biomass productivity only in the 2 L bioreactor (12%). Thus, phenolic compounds from sugarcane syrup do not influence ß-farnesene production at a large scale under the conditions tested.

Cognitive performance during senescence in untreated congenital isolated GH deficiency.

Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.

Women with Genitourinary Syndrome of Menopause Treated with Vaginal Estriol, Microablative Fractional CO2 Laser and Microablative Fractional Radiofrequency: A Randomized Pilot Study.

Objective: This pilot study intended to assess the feasibility of a large-scale randomized clinical trial designed to analyze the effectiveness of microablative fractional CO2 laser (CO2L) and microablative fractional radiofrequency (RF) compared with vaginal estriol (VE) as treatments for women with moderate-to-severe Genitourinary Syndrome of Menopause (GSM). Methods: Participants were randomized into VE, CO2L, or RF groups. In the VE group, women were required to use vaginal estriol cream for 14 days and then twice a week for 4 months. In the CO2L and RF groups, three energy therapies were administered at monthly intervals. Visual Analog Scale (VAS) for GSM symptoms, Female Sexual Function Index (FSF-I), Vaginal Health Index (VHI), and Nugent Score (NS) were analyzed before and 120 days after the beginning of the treatments. Pain scores were verified after each CO2L and RF session. Results: Thirty-four participants completed the study: 11 in the VE group, 11 in the CO2L group, and 12 in the RF group. No unexpected or serious adverse events were observed. We also verified that GSM symptoms, sexual function, and VHI significantly improved (p < 0.05) with no difference among the groups. NS did not show statistically significant difference before and after the treatments. Pain during RF application was associated with higher scores. Conclusions: The study is feasible and does not seem to have safety implications. Preliminary results suggest that CO2L and RF are good alternatives to VE for ameliorating clinical symptoms, FSF-I, and VHI in patients with GSM. Clinical Trial Registration number: NCT04045379.

The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus.

The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has antiproliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin-, nucleolus- and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription, rRNA expression and chromatin-remodeling proteins. The global transcriptional rate and nucleolus area increased along with nucleolar disorganization upon 24 h of FGF2 stimulation. FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing. RNA Pol I inhibition partially reversed the growth arrest induced by FGF2, indicating that changes in rRNA expression might be crucial for triggering the antiproliferative effect. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes and modulates the main cell transcription site, the nucleolus.