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Background Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods This single-centre, pilot randomized clinical trial was conducted at the University Hospital “Maggiore della Carità” (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration registered on the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au), registration number ACTRN12615000707561.

Aims While greater physical activity (PA) is associated with improved health outcomes, the direct links between distinct components of PA, their changes over time, and cardiorespiratory fitness are incompletely understood. Methods and results Maximum effort cardiopulmonary exercise testing (CPET) and objective PA measures [sedentary time (SED), steps/day, and moderate-vigorous PA (MVPA)] via accelerometers worn for 1 week concurrent with CPET and 7.8 years prior were obtained in 2070 Framingham Heart Study participants [age 54 ± 9 years, 51% women, SED 810 ± 83 min/day, steps/day 7737 ± 3520, MVPA 22.3 ± 20.3 min/day, peak oxygen uptake (VO2) 23.6 ± 6.9 mL/kg/min]. Adjusted for clinical risk factors, increases in steps/day and MVPA and reduced SED between the two assessments were associated with distinct aspects of cardiorespiratory fitness (measured by VO2) during initiation, early-moderate level, peak exercise, and recovery, with the highest effect estimates for MVPA (false discovery rate Conclusions Our findings provide a detailed assessment of relations of different types of PA with multidimensional cardiorespiratory fitness measures and suggest favourable longitudinal changes in PA (and MVPA in particular) are associated with greater objective fitness.

Rationale: The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not...

Background: Treatment with radium-223 has been shown to increase survival and to delay skeletal events related to bone metastases of patients with metastatic Castration Resistant Prostate Cancer (mCRPC). This treatment has also proved to be well tolerated, and hematological toxicity, in particular anemia, represents the most represented adverse event. Materials and methods: We evaluated the hematologic toxicity of Ra-223 treatment in a real-life experience of 38 patients from two Italian cancer centers, with bone metastases from mCRPC. The main endpoint of the study was the evaluation of the efficacy and tolerability of treatment with radium-223, with greater reference to hematological toxicity (especially anemia) as the cause of interruption of treatment, specifically in the elderly patient. Results: From August 2016 to October 2017, a total of 38 consecutive nonselected patients, 20 of them aged >75 years, with mCRPC symptomatic bone metastases, were enrolled for radium-223 at standard doses. Hematologic adverse events were recorded more frequently (72.4% with AE), and 36.8% had anemia. The most frequent cause of treatment discontinuation due to AEs was anemia [8/10 patients (80%)], followed by thrombocytopenia (2 patients) and neutropenia (1 patient). Hematologic AEs were more represented in elderly patients with greater disease burden and previously treated with docetaxel. Conclusions: Anemia is the most represented AE related to radium-223 treatment in elderly patients with greater disease burden and previously treated with docetaxel, besides representing the main reason for interruption of treatment. Correct patient selection, appropriate timing, and adequate supportive care are elements that could facilitate successful treatment with radium-223, preventing premature interruption of the same. The results of this experience support the opportunity to propose treatment with radium-223 mostly in patients in the earliest stages. Keywords: Cancer, Older, Prostate, Ra-223, Toxicity

Early de-tethering procedures are performed on spinal dysraphisms to prevent neuro-urological deterioration caused by growth. Partial lipoma removal may cause delayed deterioration by re-tethering, while complete removal may increase the risk of postoperative worsening. The present study evaluates the risk of postoperative deterioration and the protective potential of intraoperative neurophysiological monitoring (IOM), with a special reference to the conus lipomas treated with the radical approach. Forty toddlers (

DNA methylation has fundamental roles in gene programming and aging that may help predict mortality. However, no large-scale study has investigated whether site-specific DNA methylation predicts all-cause mortality. We used the Illumina-HumanMethylation450-BeadChip to identify blood DNA methylation sites associated with all-cause mortality for 12, 300 participants in 12 Cohorts of the Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium. Over an average 10-year follow-up, there were 2,561 deaths across the cohorts. Nine sites mapping to three intergenic and six gene-specific regions were associated with mortality (P < 9.3x10-7) independently of age and other mortality predictors. Six sites (cg14866069, cg23666362, cg20045320, cg07839457, cg07677157, cg09615688)—mapping respectively to BMPR1B, MIR1973, IFITM3, NLRC5, and two intergenic regions—were associated with reduced mortality risk. The remaining three sites (cg17086398, cg12619262, cg18424841)—mapping respectively to SERINC2, CHST12, and an intergenic region—were associated with increased mortality risk. DNA methylation at each site predicted 5%¬¬–15% of all deaths. We also assessed the causal association of those sites to age-related chronic diseases by using Mendelian randomization, identifying weak causal relationship between cg18424841 and cg09615688 with coronary heart disease. Of the nine sites, three (cg20045320, cg07839457, cg07677157) were associated with lower incidence of heart disease risk and two (cg20045320, cg07839457) with smoking and inflammation in prior CHARGE analyses. Methylation of cg20045320, cg07839457, and cg17086398 was associated with decreased expression of nearby genes (IFITM3, IRF, NLRC5, MT1, MT2, MARCKSL1) linked to immune responses and cardiometabolic diseases. These sites may serve as useful clinical tools for mortality risk assessment and preventative care.

The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sorely testing health care systems and economies around the world and is rightly considered as the major health emergency in a century. Despite the course of the disease appearing to be mild in many cases, a significant proportion of symptomatic patients develop pneumonia requiring hospitalisation or progress to manifest respiratory complications leading to intensive care treatment. Potential interventions for SARS-CoV2-associated pneumonia are being tested, some of which holding promise, but as of today none of these has yet demonstrated outstanding efficacy in treating COVID-19. In this article, we discuss fresh perspectives and insights into the potential role of immune dysregulation in COVID-19 as well as similarities with systemic inflammatory response in sepsis and the rationale for exploring novel treatment options affecting host immune response.

Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients’ parameters. The whole cohort was divided into two groups based on the age of the patients (

Background The electronic Framingham Heart Study (eFHS) is an ongoing nested study, which includes FHS study participants, examining associations between health data from mobile devices with cardiovascular risk factors and disease. Objective To describe application (app) design, report user characteristics, and describe usability and survey response rates. Methods Eligible FHS participants were consented and offered a smartwatch (Apple Watch), a digital blood pressure (BP) cuff, and the eFHS smartphone app for administering surveys remotely. We assessed usability of the new app using 2 domains (functionality, aesthetics) of the Mobile App Rating Scale (MARS) and assessed survey completion rates at baseline and 3 months. Results A total of 196 participants were recruited using the enhanced eFHS app. Of these, 97 (49.5%) completed the MARS instrument. Average age of participants was 53 ± 9 years, 51.5% were women, and 93.8% were white. Eighty-six percent of participants completed at least 1 measure on the baseline survey, and 50% completed the 3-month assessment. Overall subjective score of the app was 4.2 ± 0.7 on a scale from 1 to 5 stars. Of those who shared their health data with others, 46% shared their BP and 7.7% shared their physical activity with a health care provider. Conclusion Participants rated the new, enhanced eFHS app positively overall. Mobile app survey completion rates were high, consistent with positive in-app ratings from participants. These mobile data collection modalities offer clinicians new opportunities to engage in conversations about health behaviors.

Background: Tracheal intubation in patients with coronavirus disease-19 is a high-risk procedure that should be performed with personal protective equipment (PPE). The influence of PPE on operator’s performance during tracheal intubation remains unclear. Methods: We conducted a systematic review and meta-analysis of simulation studies to evaluate the influence of wearing PPE as compared to standard uniform regarding time-to-intubation (TTI) and success rate. Subgroup analyses were conducted according to device used and operator’s experience. Results: The TTI was prolonged when wearing PPE (eight studies): Standard Mean Difference (SMD)-0.54, 95% Confidence Interval [-0.75,-0.34], p < 0.0001. Subgroup analyses according to device used showed similar findings (direct laryngoscopy, SMD-0.63 [-0.88,-0.38], p < 0.0001; videolaryngoscopy, SMD-0.39 [-0.75,-0.02], p = 0.04). Considering the operator’s experience, non-anesthesiologists had prolonged TTI (SMD-0.75 [-0.98,-0.52], p < 0.0001) while the analysis on anesthesiologists did not show significant differences (SMD-0.25 [-0.51, 0.01], p = 0.06). The success rate of tracheal intubation was not influenced by PPE: Risk Ratio (RR) 1.02 [1.00, 1.04]; p = 0.12). Subgroup analyses according to device demonstrated similar results (direct laryngoscopy, RR 1.03 [0.99, 1.07], p = 0.15, videolaryngoscopy, RR 1.01 [0.98, 1.04], p = 0.52). Wearing PPE had a trend towards negative influence on success rate in non-anesthesiologists (RR 1.05 [1.00, 1.10], p = 0.05), but not in anesthesiologists (RR 1.00 [0.98, 1.03], p = 0.84). Trial-sequential analyses for TTI and success rate indicated robustness of both results. Conclusions: Under simulated conditions, wearing PPE delays the TTI as compared to dressing standard uniform, with no influence on the success rate. However, certainty of evidence is very low. Performing tracheal intubation with direct laryngoscopy seems influenced to a greater extent as compared to videolaryngoscopy. Similarly, wearing PPE affects more the non-anesthesiologists subgroup as compared to anesthesiologists.

Background: Intraoperative hypotension is associated with increased postoperative morbidity and mortality. Methods: We randomly assigned patients undergoing major general surgery to early warning system (EWS) and hemodynamic algorithm (intervention group,n= 20) or standard care (n= 20). The primary outcome was the difference in hypotension (defined as mean arterial pressure < 65 mmHg) and as secondary outcome surrogate markers of organ injury and oxidative stress. Results: The median number of hypotensive episodes was lower in the intervention group (−5.0 (95% CI: −9.0, −0.5);p< 0.001), with lower time spent in hypotension (−12.8 min (95% CI: −38.0, −2.3 min);p= 0.048), correspondent to −4.8% of total surgery time (95% CI: −12.7, 0.01%;p= 0.048).The median time-weighted average of hypotension was 0.12 mmHg (0.35) in the intervention group and 0.37 mmHg (1.11) in the control group, with a median difference of −0.25 mmHg (95% CI: −0.85, −0.01;p= 0.025). Neutrophil Gelatinase-Associated Lipocalin (NGAL) correlated with time-weighted average of hypotension (R = 0.32;p= 0.038) and S100B with number of hypotensive episodes, absolute time of hypotension, relative time of hypotension and time-weighted average of hypotension (p< 0.001 for all). The intervention group showed lower Neuronal Specific Enolase (NSE) and higher reduced glutathione when compared to the control group. Conclusions: The use of an EWS coupled with a hemodynamic algorithm resulted in reduced intraoperative hypotension, reduced NSE and oxidative stress.

Background: Cholesterol has a pivotal role in human physiology, exerting both structural and functional activity. However, higher blood cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), are a major cardiovascular risk factor. Therefore, special attention has been given to the effect of dietary factors in influencing LDL-C blood levels. In particular, much research has focused on dairy products, since they are a main component of different dietary patterns worldwide. A large body of evidence did not support the hypothesis that dairy products significantly increase circulating LDL-C, but no definitive data are available. Hence, we aimed to assess the relationships among LDL-C, habitual dairy food intake and anthropometric variables in a cohort representative of the general population in a Mediterranean area. Methods: We evaluated 802 healthy adults included in the ABCD_2 (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. The habitual intake of dairy products was assessed with a validated food frequency questionnaire, and LDL-C serum levels and several anthropometric parameters were measured. Results: The group with high LDL-C serum concentrations (≥130 vs. &lt, 130 mg/dL) exhibited higher age, body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage, systolic and diastolic blood pressure, carotid intima-media thickness and glycated hemoglobin. The habitual diet was not different between the groups in terms of macronutrient, cholesterol, egg and dairy food intake, with the exception of the weekly number of portions of milk (higher in the low LDL-C group vs. the high LDL-C group) and ricotta cheese (higher in the high LDL-C group vs. the LDL-C group). No significant correlation was found between LDL-C blood levels and the habitual intake of dairy products or the dietary intake of cholesterol and fats. The multivariate regression analyses (R2 = 0.94) showed that LDL-C blood levels were significantly associated with the habitual intake of milk (p &lt, 0.005) and ricotta cheese (p &lt, 0.001) and with BMI (p &lt, 0.001). Conclusion: Our study reported that total dairy food consumption was not correlated with LDL-C blood levels. However, multivariate analyses showed an inverse association between serum LDL-C and milk intake as well as a positive association between ricotta cheese intake and LDL-C concentrations. More studies are needed to better characterize the relationship between dairy products and circulating LDL-C.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p

Background: One of the mechanisms suggested to link physical activity (PA) to favorable brain health is through stimulation of neural growth factors such as brain-derived neurotrophic factor (BDNF). Acute bouts of PA stimulate circulating BDNF levels. Objective: In this investigation, we assessed whether habitual, accelerometer-measured PA levels were related to circulating BDNF levels in a middle-aged cohort. Methods: In the Framingham Heart Study Third Generation cohort, 1,769 participants provided reliable accelerometry data and were not missing BDNF measurement or platelet counts. In a cross-sectional analysis, using multivariable regression, we related PA measures to serum BDNF levels, adjusting for age, sex, smoking status, platelet count, depression status, and accelerometer wear time. Results: Our study participants (mean age 47±9 years, 50.8% women) spent an average of 22.3 mins/day in moderate-to-vigorous (MV)PA. Most PA variables (steps, MVPA, light activity, and sedentary time) were not related to BDNF levels (p > 0.05). We observed a non-linear trend, where 15–50 mins/week vigorous activity was associated with lower BDNF compared to those with 0 min vigorous activity (β= –0.049±0.024, p = 0.05), but with no significant associations at lower or higher vigorous activity levels. In smokers, MVPA was also associated with lower BDNF levels (β= –0.216±0.079, p = 0.01). Conclusion: Our study reveals that circulating BDNF is not chronically elevated in individuals with higher levels of habitual PA in middle-aged adults from the community and may even be chronically suppressed with higher PA in subgroups, including current smokers. These results do not contradict previous studies demonstrating that circulating BDNF rises acutely after PA.

Background: Intraoperative hypotension is associated with increased postoperative morbidity and mortality. We tested whether the clinical application of an early warning system (EWS) in combination with an algorithm for hemodynamic management reduces the occurrence of intraoperative hypotension as well as decrease the degree of organ injury and oxidative stress. Methods: We randomly assigned patients undergoing major general surgery EWS and hemodynamic algorithm (intervention group, n=20) or standard care (n=20). The primary outcome was the difference in hypotension (defined as mean arterial pressureResults: The median number of hypotensive episodes was lower in the intervention group [-5.0 (95%CI:-9.0,-0.5);P Conclusions: The use of an EWS coupled with an hemodynamic algorithm resulted in reduced intraoperative hypotension. This finding was coupled with a reduction of biomarkers of brain injury and oxidative stress.Trial Registration number and date: “Correlation Between Circulating Biomarkers of Organ Damage and Intraoperative Hypotension Management”, NCT03527758, registered on May 17, 2018.https://www.clinicaltrials.gov/ct2/show/NCT03527758?term=NCT03527758&draw=2&rank=1

Purpose: To assess the pain intensity of two intracameral anesthetic solutions in patients undergoing cataract surgery and evaluate the factors influencing the patients’ postoperative activities. Methods: Sixty-two patients undergoing cataract surgery were randomized to receive the study drug – a manufactured solution of 0.02% tropicamide/0.31% phenylephrine/1% lidocaine (Mydrane) or a traditional anesthetic formulation - solution of 1% lidocaine/0.025% adrenaline as an intraocular anesthetic. The pain intensity was assessed by Visual Analog Scale for Pain (VAS Pain) and Brief Pain Inventory-short form (BPI) on the next day after the surgery. Results: The mean pain score measured preoperatively with VAS Pain was 0.34 in Mydrane group and 0.09 in the reference group (p = 0.51). There were no statistically significant differences between the two anesthetic methods with respect to pain intensity during the surgery (p = 0.94) and the influence of pain during the last 24 h on activity (p = 0.79), mood (p = 0.31), social contacts (p = 0.29), sleep (p = 0.5) and the joy of life (p = 0.39). Additionally, there was no statistically significant influence of age, sex, lateralization, co-existing ophthalmological diseases (p = 0.98) and post-operative complications (p = 0.4) on the experienced pain measured during the surgery and in the last 24 h. Conclusions: New commercially available intraocular anesthetic solution (Mydrane™) seems to be as effective as off-label traditional anesthetic formulation, in reducing the pain experienced during cataract surgery under topical anesthesia.

Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5–7%, and the percentage of positive patients admitted to intensive care units being 9–11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

We read with great interest the paper by Gaudio and colleagues on vitamin D and on the state of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the time of admission [...].

Osteonecrosis of the jaw (ONJ) is a rare and severe necrotic bone disease reflecting a compromise in the body's osseous healing mechanisms and unique to the craniofacial region. Radium 223 dichloride (Ra223) is the only targeted alpha therapy able to extend survival in patients with bone metastases from prostate cancer. Mechanism of action and data currently available focused mainly on osteoblastic metastases from prostate cancer. In 2018, a Caucasian 54-year-old woman presented to our institution for a breast cancer with bone metastases. Since the patient refused any treatment and taking into account the bone disease, our multidisciplinary team evaluated a supplementary strategy with radium 223. A total of six treatments were planned with a dose of 50 KBq/kg every 4 weeks according to Phase 2 data. Four days after the second cycle administration, the patient presented for examination with a self-extracted necrotic bone fragment. Oroantral communication remained in the absence of algic symptomatology or suppuration. The multidisciplinary approach between oncologists, nuclear physicians, and dental health teams is crucial throughout the treatment process to avoid unnecessary suffering in patients at risk. More prospective studies are needed; however, considering the limitation of the present case, radio 223 may play an adjuvant role in the medical treatment of cancer patients with active ONJ.

Background:Cystic Fibrosis (CF), one of the most frequent genetic diseases, is characterized by the production of viscous mucus in several organs. In the lungs, mucus clogs the airways and traps bacteria, leading to recurrent/resistant infections and lung damage. For cystic fibrosis patients, respiratory failure is still lethal in early adulthood since available treatments display incomplete efficacy.Objective:The objective of this review is to extend the current knowledge in the field of available treatments for cystic fibrosis. A special focus has been given to inhaled peptide-based drugs.Methods:The current review is based on recent and/or relevant literature and patents already available in various scientific databases, which include PubMed, PubMed Central, Patentscope and Science Direct. The information obtained through these diverse databases is compiled, critically interpreted and presented in the current study. An in-depth but not systematic approach to the specific research question has been adopted.Results:Recently, peptides have been proposed as possible pharmacologic agents for the treatment of respiratory diseases. Of note, peptides are suitable to be administered by inhalation to maximize efficacy and reduce systemic side effects. Moreover, innovative delivery carriers have been developed for drug administration through inhalation, allowing not only protection against proteolysis, but also a prolonged and controlled release.Conclusion:Here, we summarize newly patented peptides that have been developed in the last few years and advanced technologies for inhaled drug delivery to treat cystic fibrosis.

We report on multi-wavelength ultraviolet (UV) high-resolution observations taken with the IRIS satellite during the emergence phase of an emerging flux region embedded in the unipolar plage of active region NOAA 12529. These data are complemented by measurements taken with the spectropolarimeter aboard the Hinode satellite and by observations from SDO.In the photosphere, we observe the appearance of opposite emerging polarities, separating from each other, and cancellation with a pre-existing flux concentration of the plage.In the upper atmospheric layers, recurrent brightenings resembling UV bursts, with counterparts in all UV/EUV filtergrams, are identified in the EFR site. In addition, plasma ejections are observed at chromospheric level. Most important, we unravel a signature of plasma heated up to 1 MK detecting Fe XII emission in the core of the brightening sites.Comparing these findings with previous observations and numerical models, we suggest evidence of several long-lasting, small-scale magnetic reconnection episodes between the new bipolar EFR and the ambient field.

BACKGROUND: Older adults may have difficulty meeting the Physical Activity (PA) Guidelines. A favorable balance between PA and sedentary time (SED) is an important determinant of physical performance in older adults. Our objective was to explore associations of PA/SED with physical performance across mid-older age in adults without overt mobility disability. METHODS: Framingham Offspring Study participants free of mobility disability with accelerometry and physical performance data (gait speed, chair stand time, and handgrip strength), were studied in cross-sectional analysis (n = 1352). We regressed physical performance on PA level, measured using steps, moderate to vigorous (MV) PA and SED. We stratified by age groups, adjusted for covariates, and modelled MVPA and SED separately and together as predictors. RESULTS: Only 38% of adults 50–64 years and 15% of adults ≥75 years met the PA Guidelines (i.e., 150 min MVPA per week). Individuals achieving at least 5 min/day of MVPA had 0.062 ± 0.013 m/s greater gait speed and better chair stands and handgrip strength (in women) than those with < 5 min/day of MVPA (p < 0.01) across mid-older age. SED was associated with poorer performance on gait speed and chair stand tests, but results were not significant after adjusting for MVPA (p > 0.05). For adults ≥75 years, every 5000 more steps/day related to ~0.045 m/s greater gait speed (p = 0.006). CONCLUSION: Our cross-sectional study demonstrated that, across mid-older adulthood, MVPA related to better physical performance, but in adults ≥75 years, total steps walked associated with better gait speed. These data warrant future research on the impact of PA on physical performance and health outcomes in older age.

Aims. Circulating insulin-like growth factor- (IGF-) 1, vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) levels are often lower in individuals with diabetes mellitus (DM) and are important for repairing vascular and neuronal dysfunction. The purpose of this investigation was to determine the cross-sectional relations of physical activity to circulating concentrations of IGF-1, VEGF, and BDNF in individuals with and without DM.Methods. In 1730 participants from the Framingham Offspring Study examination cycle 7, including those with DM (n=179, mean age 64 years, 39% women) and without DM (n=1551, mean age 60 years, 46% women), we related self-reported physical activity variables to circulating concentrations of IGF-1, VEGF, and BDNF using linear multivariable regression models. We also tested for interactions by age. Participants with prevalent cardiovascular disease, stroke, and dementia or taking hormone replacement therapy were excluded.Results. In participants with DM, more ambulatory physical activity was associated with higher IGF-1 levels (β±standarderrorSE=0.22±0.08,p=0.009), and more total physical activity was related to higher BDNF levels (β±SE=0.18±0.08,p=0.035), but physical activity was not significantly related to circulating VEGF. In participants without DM, no associations were observed. Moreover, in the examination of interactions by age, the association of ambulatory physical activity with IGF-1 levels was only observed in older adults with DM (age≥60years,β±SE=0.23±0.11,p=0.042) but not in middle-aged adults with DM (age<60years,β±SE=0.06±0.13,p=0.645).Conclusion. Our results suggest that more physical activity is associated with higher circulating IGF-1 and BDNF in participants with DM. These results, dissecting interactions by both age and DM status, may also help to explain some of the inconsistent results in studies relating physical activity to growth and neurotrophic factors.

Introduction Physical activity (PA) may play a role in maintenance of cognitive function in both middle and older ages and prevention of outcomes such as dementia and Alzheimer's disease. Methods Cross-sectional regression analyses were performed in Framingham Heart Study Third Generation (n = 1861) and Offspring (n = 909) cohort participants assessing the association of accelerometry-measured PA with cognitive function, adjusting for age, sex, accelerometer wear time, education, occupational status/PA, and smoking status. Results In each cohort, achieving just 10–21.4 min/day moderate-to-vigorous PA related to better executive function (P, Highlights • Physical activity related to better cognition in middle-aged and older adults. • Just 10 minutes of moderate-to-vigorous activity related to better cognition. • Walking more total steps/day is related to better executive function in older adults.

Background When studied in community-based samples, the association of physical activity with blood pressure (BP) remains controversial and is perhaps dependent on the intensity of physical activity. Prior studies have not explored the association of smartwatch-measured physical activity with home BP. Objective We aimed to study the association of habitual physical activity with home BP. Methods Consenting electronic Framingham Heart Study (eFHS) participants were provided with a study smartwatch (Apple Watch Series 0) and Bluetooth-enabled home BP cuff. Participants were instructed to wear the watch daily and transmit BP values weekly. We measured habitual physical activity as the average daily step count determined by the smartwatch. We estimated the cross-sectional association between physical activity and average home BP using linear mixed effects models adjusting for age, sex, wear time, antihypertensive drug use, and familial structure. Results We studied 660 eFHS participants (mean age 53 years, SD 9 years; 387 [58.6%] women; 602 [91.2%] White) who wore the smartwatch 5 or more hours per day for 30 or more days and transmitted three or more BP readings. The mean daily step count was 7595 (SD 2718). The mean home systolic and diastolic BP (mmHg) were 122 (SD 12) and 76 (SD 8). Every 1000 increase in the step count was associated with a 0.49 mmHg lower home systolic BP (P=.004) and 0.36 mmHg lower home diastolic BP (P=.003). The association, however, was attenuated and became statistically nonsignificant with further adjustment for BMI. Conclusions In this community-based sample of adults, higher daily habitual physical activity measured by a smartwatch was associated with a moderate, but statistically significant, reduction in home BP. Differences in BMI among study participants accounted for the majority of the observed association.

OBJECTIVES: Metabolomic markers may provide deeper insight into the underlying biology of frailty. Yet, little data exist characterizing metabolomic correlates of frailty. The objective of this cross-sectional study was to determine the association of serum metabolites with frailty. METHODS: We evaluated 2187 participants from the Framingham Offspring Study (mean age; 62y; 53% women) with metabolomic and frailty data. Metabolites (n = 217) were quantified using liquid chromatography/tandem mass spectrometry (1990–95). Frailty was assessed using Fried's frailty phenotype (1998–01). Multivariable logistic regression models were used to relate individual metabolites with odds of frailty. In 1,815 participants, we created a metabolomic signature: sum of (serum metabolite concentration*β coefficient). Metabolites were included based on the strength of their individual association with frailty (FDR ≤ 0.05). Logistic regression was used to relate the metabolomic signature with odds of frailty. C-statistics determined if the metabolomic signature improved the prediction of frailty beyond a standard model. Models were adjusted for age, sex, BMI, and smoking. RESULTS: Adjusting for age and sex, 24 metabolites were significantly associated with frailty (22 positive and 2 negative; all FDR ≤ 0.05). A majority of metabolites were lipids (n = 19) of the phosphatidylcholine (n = 7) and triacylglycerol (n = 10) sub-classes with high degree of saturation (n = 13 with

Introduction: The prevalence of obesity is rising. Most previous studies that examined the relationship between body mass index (BMI) and physical activity measured BMI at a single time-point, ignoring the time-varying nature of BMI. The relationship between BMI trajectories and habitual physical activity in community settings remains unclear. Objective: To assess the relationship between BMI trajectories and habitual physical activity measured by daily steps from a smartwatch, among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesized that participants whose BMI trajectories increased over a 14-year period prior to the step assessment take fewer daily steps, compared to participants who maintained stable BMI trajectories during the same time period. Methods: We used a semiparametric group-based modelling method to identify BMI trajectory patterns. Participants who attended exams 1, 2, and 3 were included in building the trajectories. Daily steps were recorded from the smartwatch provided at exam 3 with “active days” defined as days with ≥ 5watch wear-hours. We excluded participants with Results: We identified three trajectory groups for the 837 eFHS participants. Group 1 included 292 participants (mean age 54 years, 57% women) whose BMI was stable (slope: 0.005, p=0.75); Group 2 included 468 participants (mean age 53 years, 56% women) whose BMI increased slightly (slope: 0.123, p Conclusion: Participants whose BMI trajectory increased over time took significantly fewer steps compared to participants with more stable BMI trajectories. Our findings suggest that levels of physical activity may correlate with greater weight gain during adulthood.

Introduction: Long-term use is critical for successful clinical or research applications of digital devices, but digital health studies are challenged by significant early discontinuation of use. Hypothesis: We sought to identify factors associated with long-term use of a smartwatch among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesized that sociodemographic and health variables are associated with watch use. Methods: Participants were provided with a study smartwatch and were asked to wear the watch daily. We examined watch use over 12 months. Weekly watch use was defined as a binary response (yes=watch wear for ≥1 days for ≥ 5 hours per day, vs. no). We considered 19 different predictors including sociodemographic, health behaviors, and family relationship. We selected an individual predictor for watch use ( P Results: Among 1243 participants (mean age 53 years, 59% women), watch use was highest in the age-group ≥65 years, and decreased linearly over time in all participants (Figure). In GLMM adjusted for age, sex, and weeks, we found that self-reported health status (excellent vs good, fair or poor) (OR=2.7; 95%CI, 1.6-4.8), BMI (OR=0.9; 95%CI, 0.9-1.0) per 1 kg/m 2 increase, and depressive symptoms (OR=0.5; 95%CI, 0.3-0.8) were associated with watch use. In the model with all selected predictors, age-group > 65 (OR=4.0; 95%CI, 1.4 -11.6), excellent health (OR=2.3; 95%CI, 1.3-4.1), and depressive symptoms (OR=0.5; 95%CI, 0.3-0.9) remained significant. Conclusions: Older age, lack of depressive symptoms, and self-reported excellent health were associated with greater use of the smartwatch over the 12-month follow-up. Consideration of these factors in planning future digital studies may improve participation.

Introduction: The electronic Framingham Heart Study (eFHS) is an ongoing study nested within the Framingham Heart Study. eFHS examines associations between health data measured by mobile devices and cardiovascular risk and disease. We aim to describe the eFHS app design and deployment methodology, report the characteristics of the eFHS app users, and describe usability of the app. Hypothesis: We hypothesize that eFHS participants will find the app highly usable. Methods: Participants were eligible if they were part of FHS, had a mobile phone, and were willing to share data with the research center. After consent, they received a smartwatch, digital blood pressure (BP) cuff, and the eFHS smartphone app through which surveys were administered. Three years later, the app was enhanced to include an interactive health dashboard to promote participant engagement and facilitate survey completion. We assessed usability of the new app with the Mobile App Rating Scale (MARS) (specifically app functionality and aesthetics), and survey completion rates at baseline (measures include socio-demographics, self-reported health and health behaviors, and medical history) and 3 months (physical activity). Results: A total of 196 participants were recruited using the enhanced eFHS app. Of these, 97 (49.5%) completed the MARS. The average age of survey respondents was 53 years, 51.5% were women, 93.8% were white. At least one instrument of the baseline survey was completed by 86% of participants, and 50% completed the 3-month assessment. The mean score on the “overall impression” subscale of the MARS was 4.2 (SD 0.74) on a scale of 1 to 5, with all sub-domains scoring > 4.0. Of those who shared their health data with others, 46% shared their BP data, and 7.7% shared their physical activity data with a healthcare provider. Conclusion: Participants rated the new, enhanced eFHS app positively overall. Mobile app survey completion rates were moderate, suggesting that mHealth-delivered cardiovascular research is feasible.

Background Frailty occurs in 10-15% of community-living older adults and inflammation is a key determinant of frailty. Though diet is a modulator of inflammation, there are few prospective studies elucidating the role of diet-associated inflammation on frailty. Objective To determine whether a pro-inflammatory diet was associated with increased odds of frailty in adults from the Framingham Heart Study (FHS). Design and methods This study is nested in a prospective cohort that included individuals without frailty. Diet was assessed in 1998-2001 using a valid food frequency questionnaire (FFQ) and frailty was measured in 2011-2014. FFQ-derived energy-adjusted dietary inflammatory index (E-DII®) scores were computed, with higher E-DII scores indicating a more pro-inflammatory diet. Frailty was defined as fulfilling ≥3 of 5 Fried Phenotype criteria. Information on potential mediators, serum interleukin-6 and C-reactive protein was obtained in 1998-2001. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) for E-DII (as continuous and in quartiles) and frailty onset adjusting for relevant confounders. Results Of 1,701 individuals without frailty at baseline (mean age = 58 years, SD = 8, range: 33-81; 55% female), 224 developed frailty (13% incidence) over ∼12 years. Mean E-DII score was -1.95 (SD = 2.20; range: -6.71 to +5.40). After adjusting for relevant confounders, a one-unit higher E-DII score was associated with 16% increased odds of developing frailty (95% CI = 1.07, 1.25). In categorical analyses, participants in the highest (pro-inflammatory) vs. lowest quartile of E-DII had >2-fold increased odds of frailty (ORquartile4vs.1 = 2.22, 95% CI = 1.37, 3.60, Ptrend Conclusions In this cohort of middle-aged and older adults, a pro-inflammatory diet was associated with increased odds of frailty over ∼12 years of follow-up. Trials designed to increase consumption of anti-inflammatory foods for frailty prevention are warranted.Clinical registry number and website: Not applicable.

The coronavirus disease 2019 (COVID-19) pandemic poses a worldwide healthcare challenge that needs an efficient response. Unfortunately, to date there is no highly effective treatment, so a deep understanding of COVID-19 risk factors could be an important step in treating the disease. Vitamin D affects the immune system in many different ways, and other authors already found that COVID-19 patients have low levels of vitamin D. In our retrospective study, we evaluated the vitamin D status at the time of hospital admission in 50 COVID-19 patients in Sicily, which is the southernmost region of Italy, and compared them with 100 control subjects matched for age and sex. Our data showed markedly low levels of vitamin D in patients with a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but no association was found with inflammation markers or clinical severity. Vitamin D levels were reduced at the time of hospital admission in Sicilian SARS-CoV-2-positive patients, but it is not clear whether this condition has an impact on the clinical course of COVID-19.

Clonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA‐methylation modifying enzymes DNMT3A or TET2. We used DNA‐methylation array and whole‐genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.31 years (GrimAge, p 0 in both Hannum and GrimAge (referred to as AgeAccelHG+). This group was at high risk of all‐cause mortality (hazard ratio 2.90, p, Clonal hematopoiesis of indeterminate potential (CHIP) and epigenetic age acceleration are the two important aging phenomenon associated with adverse clinical outcomes. We found that mutations in most CHIP genes were associated with increased age acceleration in multiple epigenetic clocks. Individuals with CHIP and age acceleration had a greatly increased risk of mortality and coronary heart disease compared to individuals with only CHIP or age acceleration.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10−17), arthritis (GDF5 p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing., Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.

BackgroundeCohort studies offer an efficient approach for data collection. However, eCohort studies are challenged by volunteer bias and low adherence. We designed an eCohort embedded in the Framingham Heart Study (eFHS) to address these challenges and to compare the digital data to traditional data collection.ObjectiveThe aim of this study was to evaluate adherence of the eFHS app-based surveys deployed at baseline (time of enrollment in the eCohort) and every 3 months up to 1 year, and to compare baseline digital surveys with surveys collected at the research center.MethodsWe defined adherence rates as the proportion of participants who completed at least one survey at a given 3-month period and computed adherence rates for each 3-month period. To evaluate agreement, we compared several baseline measures obtained in the eFHS app survey to those obtained at the in-person research center exam using the concordance correlation coefficient (CCC).ResultsAmong the 1948 eFHS participants (mean age 53, SD 9 years; 57% women), we found high adherence to baseline surveys (89%) and a decrease in adherence over time (58% at 3 months, 52% at 6 months, 41% at 9 months, and 40% at 12 months). eFHS participants who returned surveys were more likely to be women (adjusted odds ratio [aOR] 1.58, 95% CI 1.18-2.11) and less likely to be smokers (aOR 0.53, 95% CI 0.32-0.90). Compared to in-person exam data, we observed moderate agreement for baseline app-based surveys of the Physical Activity Index (mean difference 2.27, CCC=0.56), and high agreement for average drinks per week (mean difference 0.54, CCC=0.82) and depressive symptoms scores (mean difference 0.03, CCC=0.77).ConclusionsWe observed that eFHS participants had a high survey return at baseline and each 3-month survey period over the 12 months of follow up. We observed moderate to high agreement between digital and research center measures for several types of surveys, including physical activity, depressive symptoms, and alcohol use. Thus, this digital data collection mechanism is a promising tool to collect data related to cardiovascular disease and its risk factors.

Aim Predicting the return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation in victims of cardiac arrest (CA) remains challenging. Cerebral regional oxygen saturation (rSO2) measured during resuscitation is feasible, and higher initial and overall values seem associated with ROSC. However, these observations were limited to the analysis of few small single-centre studies. There is a growing number of studies evaluating the role of cerebral rSO2 in the prediction of ROSC. Methods We conducted an updated meta-analysis aimed at investigating the association of initial and overall values of cerebral rSO2 with ROSC after CA. We performed subgroups analyses according to the location of CA and conducted a secondary analysis according to the country where the study was conducted (resuscitation practice varies greatly for out-of-hospital CA). Results We included 17 studies. Higher initial rSO2 values (11 studies, n = 2870, 16.6% achieved ROSC) were associated with ROSC: Mean Difference (MD) -11.54 [95%Confidence Interval (CI)-20.96, -2.12]; p = 0.02 (I2 = 97%). The secondary analysis confirmed this finding when pooling together European and USA studies, but did not for Japanese studies (p = 0.06). One multi-centre Japanese study was an outlier with large influence on 95%CI. Higher overall rSO2 values during resuscitation (9 studies, n = 894, 33.7% achieving ROSC) were associated with ROSC: MD-10.38; [-13.73, -7.03]; p Conclusions This updated meta-analysis confirmed the association between higher initial and overall values of cerebral rSO2 and ROSC after CA. However, we found geographical differences, since this association was not present when Japanese studies were analysed separately. Keywords near infrared spectrometry; advanced cardiac life support; resuscitation order; cardiopulmonary resuscitation.

Background Inappropriate authors’ self-citation (A-SC) is a growing mal-practice possibly boosted by the raising importance given to author’s metrics. Similarly, also excessive journals’ self-citation (J-SC) practice may factitiously influence journal’s metrics (impact factor, IF). Evaluating the appropriateness of each self-citation remains challenging. Main body We evaluated the presence of policies discouraging A-SC in Critical Care Medicine (CCM) journals with IF. We also calculated the J-SC rate of these journals. In order to evaluate if J-SC rates are influenced by the focus of interest of CCM journals, we separated them in three sub-categories (“multidisciplinary”, “broad” or “topic-specific” CCM journals). We analyzed 35 CCM journals and only 5 (14.3%) discouraged excessive and inappropriate A-SC. The median IF was higher in CCM journals with A-SC policies [4.1 (3–12)] as compared to those without [2.5 (2–3.5); p = 0.02]. The J-SC rate was highly variable (0–35.4%), and not influenced by the presence of A-SC policies (p = 0.32). However, J-SC rate was different according to the focus of interest (p = 0.01): in particular, it was higher in “topic-specific” CCM journals [15.3 (8.8–23.3%)], followed by “broad” CCM [11.8 (4.8–17.9%)] and “multidisciplinary” journals [6.1 (3.6–9.1%)]. Conclusions A limited number of CCM journals have policies for limiting A-SC, and these have higher IF. The J-SC rate among CCM journals is highly variable and higher in “topic-specific” interest CCM journals. Excluding self-referencing practice from scientific metrics calculation could be valuable to tackle this scientific malpractice.

Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7–12%. Single-variant analyses identified ten handgrip strength loci among African-Americans: four rare variants, five low-frequency variants, and one common variant. One significant and four suggestive genes were identified associated with handgrip strength when aggregating rare and functional variants; all associations were ancestry-specific. We additionally leveraged the different ancestries available in the UK Biobank to further explore the ancestry-specific association signals from the single-variant association analyses. In conclusion, our study identified 11 new loci associated with handgrip strength with rare and/or ancestry-specific genetic variations, highlighting the added value of whole-genome sequencing in diverse samples. Several of the associations identified using single-variant or aggregate analyses lie in genes with a function relevant to the brain or muscle or were reported to be associated with muscle or age-related traits. Further studies in samples with sequence data and diverse ancestries are needed to confirm these findings.

Carnosine is a natural occurring endogenous dipeptide that was proposed as an anti-aging agent more than 20 years ago. Carnosine can be found at low millimolar concentrations at brain level and different preclinical studies have demonstrated its antioxidant, anti-inflammatory, and anti-aggregation activity with neuroprotective effects in animal models of Alzheimer’s disease (AD). A selective deficit of carnosine has also been linked to cognitive decline in AD. Different clinical studies have been conducted to evaluate the impact of carnosine supplementation against cognitive decline in elderly and AD subjects. We conducted a systematic review with meta-analysis, in accordance with the PRISMA guidelines coupled to the PICOS approach, to investigate the therapeutic potential of carnosine against cognitive decline and depressive symptoms in elderly subjects. We found five studies matching the selection criteria. Carnosine/anserine was administered for 12 weeks at a dose of 1 g/day and improved global cognitive function, whereas no effects were detected on depressive symptoms. These data suggest a preliminary evidence of clinical efficacy of carnosine against cognitive decline both in elderly subjects and mild cognitive impairment (MCI) patients, although larger and long-term clinical studies are needed in MCI patients (with or without depression) to confirm the therapeutic potential of carnosine.

The aim of the present study was to analyze the association among systemic sclerosis (SSc), periodontitis (PT), we also evaluated the impact of PT and SSc on vitamin D levels. Moreover, we tested the association with potential confounders. A total of 38 patients with SSc, 40 subjects with PT, 41 subjects with both PT and SSc, and 41 healthy controls were included in the study. The median vitamin D levels in PT subject were 19.1 (17.6–26.8) ng/mL, while SSc + PT group had vitamin d levels of 15.9 (14.7–16.9) ng/mL, significantly lower with respect to SSc patients (21.1 (15.4–22.9) ng/mL) and to healthy subjects (30.5 (28.8–32.3) ng/mL) (p &lt, 0.001). In all subjects, vitamin D was negatively associated with c-reactive protein (CRP) (p &lt, 0.001) and with probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque score (PI) (p &lt, 0.001 for all parameters) and positively related to the number of teeth (p &lt, 0.001). Moreover, univariate regression analysis demonstrated an association among high low-density lipoproteins (LDL) cholesterol (p = 0.021), CRP (p = 0.014), and PT (p &lt, 0.001) and reduced levels of vitamin D. The multivariate regression analysis showed that PT (p = 0.011) and CRP (p = 0.031) were both predictors of vitamin D levels. Subjects with PT and SSc plus PT had significant lower vitamin D values with respect to SSc and to healthy subjects. In addition, PT seems negatively associated with levels of vitamin D in all analyzed patients.

The aim of this study was to analyze and identify the association among salivary interleukin-6 (IL-6) levels and periodontitis (PT) and to determine the significant trend of this association in PT patients.For the present study, 49 patients with PT and 47 healthy subjects (HS) were enrolled and assessed for clinical parameters, blood samples and salivary IL-6 analyses. Clinical differences among groups were recorded and evaluated. The Spearman Correlation and the Jonckheere-Terpstra Test were applied in order to assess the interdependence between salivary IL-6 and PT.Patients in the PT group had significantly higher median salivary IL-6 levels [195.4 (184.6-205.9 pg/mL)] compared to the HS group [101.9 (89.5-115.4 pg/mL) (p0.001). Salivary IL-6 levels were negatively correlated with C-reactive protein, with the number of teeth and with clinical attachment loss (CAL), probing pocket depth (PPD), and bleeding sites (FMBS) (p0.001). Furthermore, in patients with PT, salivary IL-6 levels were inversely associated (P-trend) with the number of teeth (p0.001), and directly associated with the proportional extent of PT (CAL, p = 0.006; PPD, p = 0.009; FMBS, p0.001).The results of this study showed that PT patients presented significant higher salivary IL-6 levels compared to HS. Moreover, in the analyzed sample a significant p-trend among PT, tooth loss and increased salivary IL-6 levels was found.