Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.

Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO2-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO2-OA) preferentially accumulates in WAT and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO2-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO2-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2fl/fl) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO2-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO2-OA for 48 days), both HFD-fed Nrf2fl/fl and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO2-OA treatment, no distinction was observed between Nrf2fl/fl and ANKO in the HFD-fed mice as well as in the Nrf2fl/fl mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2fl/fl and ANKO compared to LFD-fed Nrf2fl/fl mice. Notably, NO2-OA treatment improved glucose tolerance in HFD-fed Nrf2fl/fl but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO2-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.

Vaginal laser therapy for GSM/VVA: where we stand now - a review by the EUGA Working Group on Laser.

Vulvovaginal atrophy (VVA) is a chronic progressive condition that involves the genital and lower urinary tracts, related to the decrease of serum estrogenic levels when menopause occurs. The definition of genitourinary syndrome of menopause (GSM) is a medically more accurate, all-encompassing and publicly acceptable term than VVA. Due to the chronic progressive trend of GSM, symptoms tend to reappear after the cessation of therapy, and frequently long-term treatment is required. First-line therapies include vulvar and vaginal lubricant or moisturizers, and, in the case of failure, low-dose vaginal estrogens are the preferred pharmacological therapy. Populations of patients, such as breast cancer (BC) survivors, are affected by iatrogenic GSM symptoms with concerns about the use of hormonal therapies. The non-ablative erbium:YAG laser and the fractional microablative CO2 vaginal laser are the two main lasers evaluated for GSM treatment. The aim of this comprehensive review is to report the efficacy and safety of Er:YAG and CO2 vaginal lasers for GSM treatment. Vaginal laser therapy has been demonstrated to be effective in restoring vaginal health, improving VVA symptoms and sexual function. The data suggest that both Er:YAG and CO2 vaginal lasers are safe energy-based therapeutic options for management of VVA and/or GSM symptoms in postmenopausal women and BC survivors.

Long-term clinical and histological safety and efficacy of the CO2 laser for treatment of genitourinary syndrome of menopause: an original study.

OBJECTIVE: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. METHODS: A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire - Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. RESULTS: At 4 weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. CONCLUSIONS: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04868812 (release date: 27 April 2021).

Protective effects of spironolactone on vascular calcification in chronic kidney disease.

BACKGROUND: Vascular calcification is common in chronic kidney disease (CKD) and associated with increased cardiovascular mortality. Aldosterone has been implicated as an augmenting factor in the progression of vascular calcification. The present study further explored putative beneficial effects of aldosterone inhibition by the mineralocorticoid receptor antagonist spironolactone on vascular calcification in CKD. METHODS: Serum calcification propensity was determined in serum samples from the MiREnDa trial, a prospective, randomized controlled clinical trial to investigate efficacy and safety of spironolactone in maintenance hemodialysis patients. Experiments were conducted in mice with subtotal nephrectomy and cholecalciferol treatment, and in calcifying primary human aortic smooth muscle cells (HAoSMCs). RESULTS: Serum calcification propensity was improved by spironolactone treatment in patients on hemodialysis from the MiREnDa trial. In mouse models and HAoSMCs, spironolactone treatment ameliorated vascular calcification and expression of osteogenic markers. CONCLUSIONS: These observations support a putative benefit of spironolactone treatment in CKD-associated vascular calcification. Further research is required to investigate possible improvements in cardiovascular outcomes by spironolactone and whether the benefits outweigh the risks in patients with CKD.

CO2 laser and the genitourinary syndrome of menopause: a randomized sham-controlled trial.

PURPOSE: This study aimed to clarify the efficacy of intravaginal CO2-laser treatment in postmenopausal women with genitourinary syndrome of menopause (GSM). MATERIALS AND METHODS: This double-blind, randomized, sham-controlled trial included postmenopausal women diagnosed with GSM and bothersome dryness and dyspareunia. Treatment consisted of three sessions. Active CO2-laser treatments (active group) were compared to sham treatments (sham group) with the primary endpoints being changes in dryness and dyspareunia intensity, as assessed by the 10-cm visual analog scale. Secondary endpoints were as follows: changes in Female Sexual Function Index (FSFI; total score and all domains), itching, burning, dysuria, and Urogenital Distress Inventory (UDI-6); incidence of symptoms; and presence of adverse events. All outcomes were evaluated at baseline and 4 months post baseline. RESULTS: Fifty-eight women (28 in the active group and 30 in the sham group) were eligible for inclusion. In the active group, dryness, dyspareunia, FSFI (total score), itching, burning, dysuria, and UDI-6 were significantly improved (mean [standard deviation] -5.6 [2.8], -6 [2.6], 12.3 [8.9], -2.9 [2.8], -2.3 [2.8], -0.9 [2.1], and -8.0 [15.3], respectively). In the sham group, dryness, itching, and burning were significantly improved (-1.9 [2], -1.4 [1.9], and -1 [1.9], respectively). All changes were in favor of the active group. After completion of the protocol, the proportion of participants with dryness, dyspareunia, and sexual dysfunction was significantly lower in the active group compared to those in the sham group (all p < 0.005). CONCLUSIONS: CO2 laser could be proposed as an effective alternative treatment for the management of GSM as it is superior to sham treatments.

Validation of a novel smart drilling system to monitor bone impedance during transpedicular screw placement: a pilot study.

Transpedicular screw placement is a high-risk procedure routinely performed in spine surgery. To decrease the rate of complications, it is necessary to find innovative solutions to assist the surgeon during screw insertion so as to avoid the chance of mispositioning. In this study, we developed a new drilling system able to estimate the mechanical properties of drilled tissues. Several investigations show that cortical bone requires a high level of thrust force and torque during drilling compared to trabecular bone. To implement an algorithm for bony breakthrough detection, a new drilling system has been built together with a mechanical support to drill the pedicle along a pre-planned trajectory. The mechanical support is equipped with a smart rotative drill that embeds force and position sensors. Ten human vertebral segments have been used to test the surgical platform, for percutaneous bone drilling. 10 transpedicular holes from L1 to L5 have been performed bilaterally. The holes were further evaluated by computed tomographic scans to measure bone density in the cortical and in the trabecular layers. To compare bone density with the bony mechanical impedance two new parameters (DHU and DPAI) have been introduced. The results show that in 18 out of 20 cases the D values of bone density and mechanical impedance, related to the same bone transition, differ less than 10%. The proposed system is thus able to evaluate the variation of bone density of the cortical and the trabecular layer using impedance. Therefore, it is possible to use the described system to increase the accuracy of transpedicular screw placement.

Online survey of genital and urinary symptoms among Japanese women aged between 40 and 90 years.

OBJECTIVE: The purpose of this survey was to assess the prevalence of genital and urinary tract symptoms among Japanese women with declining estrogen levels. METHODS: A health-related questionnaire survey was conducted among women in their 40s or older to inquire about their genital, intercourse-related, and urinary symptoms and concern over their symptoms. RESULTS: Of the consecutive 10,000 respondents recruited, 4488 (44.9%) reported having symptoms: 3546 (79.0%) expressed concern over their symptoms. Furthermore, 2173 women (21.7%) had incontinence, 1999 (20.0%) had urinary frequency, 1648 (16.5%) had itching, and 1560 (15.6%) reported odor; these were followed by looseness, dryness, and burning. Of the 2518 (25.2%) sexually active women, 518 (20.6%) reported having dyspareunia and more reported having urinary symptoms than genital symptoms. Of the symptomatic respondents, 33.1% had genital symptoms alone, 28.4% had urinary symptoms alone, and 38.4% had both. More sexually active women had genital symptoms, while more sexually inactive women had urinary symptoms. CONCLUSIONS: Genital and urinary symptoms were shown to be common and coexist in a considerable proportion of the respondents, highlighting the pathology of genitourinary syndrome of menopause. Again, dyspareunia and lower urinary tract symptoms were shown to be quite common among postmenopausal women.

The combined use of platelet rich plasma and hyaluronic acid: prospective results for the treatment of knee osteoarthritis.

Osteoarthritis represents an important social economic burden with a high incidence worldwide. Conservative management of knee OA consists in several therapeutic options: pharmacologic therapy such as analgesics, non-steroid and steroid anti-inflammatory drugs, physical therapy, and injective therapy with hyaluronic acid (HA) and platelet-rich plasma injections (PRP). The aim of our study is to evaluate the effect of combined autologous PRP and HHA (Hybrid Hyaluronic Acid) viscosupplementation on clinical outcomes of patients with knee OA, by assessing the subjects before and after injective treatment. The study was conducted on 60 patients with an age between 40 and 70 years old affected by unilateral symptomatic knee osteoarthritis (stage II and III of Kellgren-Lawrence scale) nonresponsive to pharmacologic and rehab treatment. We divided the patients in two groups, and we treated the group A with injection of HHA and group B with HHA+PRP. Each patient received 3 injections at an interval of 1 week for 3 consecutive weeks. The patients were evaluated by the Knee Injury and Osteroartrhitis Outcome Score (KOOS) and Visual Analog Scale (VAS) at 3, 6 and 12 months after treatment. Statistical comparison between groups showed a significantly better result for the group B concerning the KOOS value, at 3 months and at 6 months. This difference, although clinically relevant, lost the statistical significance at 12 months. The VAS trend differently showed a significant difference at 3 and 12 months, while at 6 months the superiority of group B did not achieve statistical significance. Few studies investigated the effects of HA+PRP combined treatment for knee OA. Numerous studies demonstrated the efficacy of HA injection therapy in knee OA for a clinical point of view, reducing the pain and improving the quality of life. PRP preparations also improved functional outcome scores compared to hyaluronic acid and placebo in patients affected by knee OA. Based on our results we can conclude that the combined PRP and HHA treatment is not only a safe and efficacious procedure which can provide functional benefit but is also significantly better than HHA injective therapy alone, as demonstrated by the comparison within our cohort.

Impact of vulvovaginal atrophy of menopause: prevalence and symptoms in Italian women according to the EVES study.

This cross-sectional study included postmenopausal women, aged 45-75 years, with the aim to assess the presence of vulvovaginal atrophy (VVA) confirmed by a clinical assessment in the Italian population attending menopausal/gynecological centers. Apart from baseline variables, women scored vaginal, vulvar and urinary VVA symptoms. Impact of VVA on sexual function and quality of life (QoL) was assessed thorough EuroQoL questionnaire (EQ5D3L), Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-revised (FSDS-R). A physical examination was carried out in accordance with routine gynecological practice. VVA was confirmed in 90% of the 1226 evaluable patients (aged 59.0 ± 7.3 years). The prevalence of postmenopausal women with VVA confirmed by gynecological clinical assessment was 75.3%. The patients with VVA confirmed (n = 926) had more severe symptoms (p < .0005), lower QoL (EQ-visual analog scale, p = .008 and DIVA, p < .0005) and worsened sexual function (FSFI and FSDS-R, p < .0005 for both) when compared with the patients having nonconfirmed VVA (n = 140). VVA is highly prevalent among postmenopausal Italian women. The objective of VVA confirmation is associated with severe symptoms and impaired QoL and sexual function. A proactive approach of Italian clinicians to promote regular and early gynecological evaluation should be performed in order to delay the advancing of the disorder.

Finding our way through phenotypes.

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

BACKGROUND: Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO2 -FAs), such as nitro oleic acid (OA-NO2 ) and nitro linoleic acid (LNO2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. METHODS: We evaluated the effect of OA-NO2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. RESULTS: We found that subcutaneous (SC) OA-NO2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. CONCLUSION: Overall, these results support the development of OA-NO2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases.

A component-by-component characterisation of high-risk atherosclerotic plaques by multiphoton microscopic imaging.

AIMS: Atherosclerotic plaques vulnerable to rupture are almost always inflamed, and carry a large lipid core covered by a thin fibrous cap. The other components may include neovascularisation, intraplaque haemorrhage and spotty calcification. In contrast, stable plaques are characterised by a predominance of smooth muscle cells and collagen, and lipid core is usually deep seated or absent. This study is a proof of principle experiment to evaluate the feasibility of multiphoton microscopy (MPM) to identify aforementioned plaque components. METHODS AND RESULTS: MPM is a nonlinear optical technique that allows imaging based on intrinsic tissue signals including autofluorescence and higher-order scattering. In our study, MPM imaging was performed on morphologically diverse aortic and coronary artery plaques obtained during autopsy. Various histologically verified plaque components including macrophages, cholesterol crystals, haemorrhage, collagen and calcification were recognised by MPM. CONCLUSIONS: Recognition of the distinct signatures of various plaque components suggests that MPM has the potential to offer next-generation characterisation of atherosclerotic plaques. The higher lateral resolution (comparable to histology) images generated by MPM for identifying plaque components might complement larger field of view and greater imaging depth currently available with optical coherence tomography imaging. As the next step MPM would need to be evaluated for intact vessel imaging ex vivo and in vivo.

A new hyaluronic acid polymer in the augmentation and restoration of labia majora.

Aesthetic surgery of female external genitalia has gained increasing popularity over the past decade, with reduction of the labia minora (labiaplasty) being the procedure most commonly requested and performed. Female external genitalia lose elasticity and volume with age, but few studies describe the techniques for labia majora augmentation. Currently, very few studies have investigated the effectiveness and safety of labia majora augmentation with hyaluronic acid (HA) injection. This study aims to evaluate the effectiveness and safety of labia majora augmentation with hyaluronic acid filler injection. We retrospectively analyzed 37 patients affected by hypotrophy of the labia majora, treated with HA dermal filler 28mg/ml PEG crosslinked (Neauvia® Intense Rose, Matex Lab, Switzerland) between May 2015 and July 2016. Global evaluation of the aesthetics of the intimate area and clinical data were investigated with VAS (Visual Analogic Scale) ad hoc. Adverse events and complications were recorded. A total of 37 women affected by labia majora hypotrophy were treated with 28mg/ml HA dermal filler. A significant clinical improvement was observed in the score provided by both patients and doctor. Only mild adverse events and complications were recorded. HA hydrogel with a novel crosslinking agent is able to provide a considerable rejuvenation with a simple outpatient procedure and to bring a significant clinical improvement. HA-based filler infiltration treatment in labia majora is repeatable, has virtually no complications, and is reversible.

The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women.

OBJECTIVES: To assess the effect of microablative fractional CO2 laser (MFCO2-Laser) therapy on the vaginal microenvironment of postmenopausal women. METHODS: Three laser therapies at monthly intervals were applied in postmenopausal women with moderate to severe symptoms of genitourinary syndrome of menopause, pH of vaginal fluid >4.5 and superficial epithelial cells on vaginal smear <5%. Vaginal fluid pH values, fresh wet mount microscopy, Gram stain and aerobic and anaerobic cultures were evaluated at baseline and 1 month after each subsequent therapy. Nugent score and Hay-Ison criteria were used to evaluate vaginal flora. RESULTS: Fifty-three women (mean age 57.2 ± 5.4 years) participated and completed this study. MFCO2-Laser therapy increased Lactobacillus (p < 0.001) and normal flora (p < 0.001) after the completion of the therapeutic protocol, which decreased vaginal pH from a mean of 5.5 ± 0.8 (initial value) to 4.7 ± 0.5 (p < 0.001). The prevalence of Lactobacillus changed from 30% initially to 79% after the last treatment. Clinical signs and symptoms of bacterial vaginosis, aerobic vaginitis or candidiasis did not appear in any participant. CONCLUSION: MFCO2-Laser therapy is a promising treatment for improving the vaginal health of postmenopausal women by helping repopulate the vagina with normally existing Lactobacillus species and reconstituting the normal flora to premenopausal status.

Low mean impedance in 24-hour tracings and esophagitis in children: a strong connection.

Esophageal multiple intraluminal impedance baseline is an additional impedance parameter that was recently related to esophageal integrity. The aim of this study was to assess the relationship between mean esophageal impedance value and endoscopic findings in a large group of children. Children with symptoms of gastroesophageal reflux submitted to both endoscopy and impedance were included. Esophagitis was graded according to the Los Angeles classification. Mean impedance value was automatically calculated over 24-hour tracings. Data were adjusted for age through z-score transformation using percentiles normalized by the LMS (Lambda for the skew, Mu for the median, and Sigma for the generalized coefficient of variation) method. Nonparametric Mann-Whitney and Kruskal-Wallis tests, multiple, and stepwise regression were used. P-value <0.05 was considered as statistically significant. A total of 298 impedance tracings were analyzed. Endoscopic and histological esophagitis were detected in 30 and 29% patients, respectively. Median baseline z-score was significantly decreased both in proximal (P = 0.02) and distal (P = 0.01) esophagus in patients with endoscopic (but not histological) esophagitis. Patients with more severe esophagitis showed the lowest z-score. Bolus exposure index and the number of reflux episodes were the variables that were significantly associated with the baseline z-score. Impedance z-score is significantly decreased in infants and children with endoscopic esophagitis. Severity of esophagitis, bolus exposure index, and number of reflux episodes are factors influencing mean esophageal impedance.

Sexual function after fractional microablative CO2 laser in women with vulvovaginal atrophy.

OBJECTIVE: To investigate the effects of fractional microablative CO2 laser on sexual function and overall satisfaction with sexual life in postmenopausal women with vulvovaginal atrophy (VVA). METHOD: This prospective study included 77 postmenopausal women (mean age 60.6 ± 6.2 years) treated for VVA symptoms with the fractional microablative CO2 laser system (SmartXide(2) V(2)LR, Monalisa Touch, DEKA, Florence, Italy). Sexual function and quality of life were evaluated with the Female Sexual Function Index (FSFI) and the Short Form 12 (SF-12), respectively, both at baseline and at 12-week follow-up. A 10-mm visual analog scale was used to measure the overall satisfaction with sexual life and the intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia and dysuria) before and after the study period. RESULTS: We observed a significant improvement in the total score and the scores in each specific domain of the FSFI at 12-week follow-up compared to baseline (p < 0.001). After concluding the laser treatment, the overall satisfaction with sexual life significantly improved (p < 0.001). Seventeen (85%) out of 20 (26%) women, not sexually active because of VVA severity at baseline, regained a normal sexual life at the 12-week follow-up. Finally, we also found a significant improvement in each VVA symptom (p < 0.001) and in quality-of-life evaluation, both for the scores in the physical (p = 0.013) and mental (p = 0.002) domains. CONCLUSIONS: Fractional microablative CO2 laser treatment is associated with a significant improvement of sexual function and satisfaction with sexual life in postmenopausal women with VVA symptoms.

ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease.

The genotype distribution of two gene polymorphisms, previously associated with peripheral artery disease (PAD), has been evaluated in a population of diabetic (DPAD) and non-diabetic (NDPAD) patients affected by symptomatic PAD (stages II-IV). A decreased frequency of the AA genotype of rs5498 (ICAM-1) was observed in the PAD subjects compared to controls but this result did not reach statistical significance (p=0.06 by chi-squared test). On the contrary, a significant increase in the frequency of the GG homozygous genotype of rs248793 (SRD5A1) was observed in the PAD patient group in comparison to controls (p=0.01). These data confirm that the GG genotype of rs248793 in the SRD5A1 gene is significantly associated with symptomatic PAD and show a trend towards a stronger association with the non-diabetic status.

A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study.

OBJECTIVE: This pilot study aimed to assess the efficacy and feasibility of fractional CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA symptoms were assessed before and after three applications of laser over 12 weeks in 50 women (age 59.6 ± 5.8 years) dissatisfied with previous local estrogen therapies. Subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures were used during the study period to assess VVA. Quality of life was measured by using the SF-12. A subjective scale to evaluate the degree of pain related to the laser application and the degree of difficulty to perform the laser procedure was used. RESULTS: Fractional CO2 laser treatment was effective to improve VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia, dysuria; p < 0.001) at 12-week follow-up, as well as the VHIS (13.1 ± 2.5 at baseline vs. 23.1 ± 1.9; p < 0.001). Both physical and mental scores of quality of life were significantly improved in comparison with baseline (p < 0.001). Satisfaction with the laser procedure was reported by 42 women (84%) and a minimal discomfort was experienced at the first laser application, mainly because of the insertion and the movements of the probe. Finally, the technique was very easy to perform in all women starting from the second application at week 4 and no adverse events were recorded during the study period. CONCLUSIONS: A 12-week treatment with the fractional CO2 laser was feasible and induced a significant improvement of VVA symptoms by ameliorating vaginal health in postmenopausal women. Further controlled studies should be performed to confirm the present data and to assess the long-term effects of the laser procedure on vaginal tissues.

Behind the (impedance) baseline in children.

Impedance baseline is a new parameter recently related to esophageal integrity. The aim of this study was to assess the effect of different factors on impedance baseline in pediatric patients. We analyzed the impedance baseline of 800 children with symptoms of gastroesophageal reflux. Mean impedance baseline was automatically calculated throughout 24-hour tracings. The presence of different age groups and of esophagitis was evaluated. Unpaired t-test, Spearman rank correlation, polynomial, and regression plot were used for statistical analysis. Age-related percentile curves were created. We considered a P-value<0.05 as statistically significant. Impedance baseline was significantly (P<0.001) lower in younger compared to older children up to 48 months. The mean increase of baseline per month was much higher in the first 36 months of life (47.5 vs. 2.9 Ohm in Channel 1 and 29.9 vs. 2.3 Ohm in Channel 6, respectively) than in older ages. Patients with esophagitis showed significantly decreased impedance baseline (P<0.05). Infants (especially in the first months of life) and young children present a significantly lower impedance baseline compared to older children both in proximal and distal esophagus. The presence of esophagitis may also determine a decreased impedance baseline regardless of the age of the patients.