Impact of Inflammatory Markers and Senescence-Associated Secretory Phenotype in the Gingival Crevicular Fluid on the Outcomes of Periodontal Regeneration.

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1ß, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1ß and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.

Influence of locally delivered doxycycline on the clinical and molecular inflammatory status of intrabony defects prior to periodontal regeneration: A double-blind randomized controlled trial.

OBJECTIVES: To test the effect of locally delivered doxycycline (DOX) administered 2 weeks prior to minimally invasive periodontal regeneration in terms of presurgical inflammatory status and cytokine expression profile in the gingival crevicular fluid (GCF). Secondary aim was to assess the early wound healing index (EHI) at 2 weeks after surgery. BACKGROUND: It is hypothesized that healing after periodontal regeneration is dependent on preoperative soft tissue condition, and that local antibiotics may improve the site-specific inflammatory status at short time. METHODS: Sites associated with periodontal intrabony defects requiring regenerative surgery and showing bleeding on probing (BoP) were included. At T0, experimental sites were randomly treated with subgingival instrumentation with or without topic DOX application. After 2 weeks (T1), defects were approached by means of minimally invasive surgical technique. GCF was sampled at both T0 and T1 for inflammatory biomarker analysis. Two weeks after surgery, the EHI was evaluated (T2). RESULTS: Forty-four patients were included. At T1, the number of BoP+ sites was statistically significantly less in the test group (27.3% vs. 72.7%; p < .01). The total amount of interleukin (IL)-1ß (p < .001), matrix-metalloproteinases (MMP)-8 (p < .001), and MMP-9 (p = .010) in the GCF significantly decreased in the test group at T1, with relevant differences compared to controls. At T2, the EHI had an average value of 1.45 ± 0.86 in the test group while in the control, it was 2.31 ± 1.43 (p = .027). A statistically significantly positive correlation was observed between the amount of IL-1ß and MMP-9 and EHI scores. CONCLUSIONS: Within the limitations of this study, sites treated with DOX showed improved clinical and molecular inflammatory parameters before surgery, as well as soft tissue healing 2 weeks after surgery.

Experimental pseudo-equivalent deterministic excitation method extension for low frequency domain applications.

In transport engineering applications, flow-induced vibrations is an interesting topic to address since it may negatively affect the operation and the response of the system. Wind tunnel facilities are mandatory to test the structure design efficiency or to analyse new material performances under aerodynamic load. However, these experimental tests can be expensive and take a long time to set up and operate; hence, alternative methods for the reproduction of the structural response to a turbulent boundary layer excitation are required to accelerate and improve the experimental setups and provide more data for uncertainty analysis. In this paper, an alternative approach, the eXperimental Pseudo-Equivalent Deterministic Excitation method (X-PEDEM), is here extended for applications in the low frequency domain. An investigation about the applicability of the method in the low frequency domain is conducted, together with an analysis of its main properties. The reliability of the method is then tested numerically by considering different conditions: two different panels, two different boundary conditions, and different asymptotic flow velocities are considered.

Cystatin SN (CST1) as a Novel Salivary Biomarker of Periodontitis.

Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed as having periodontally healthy conditions (H), severe periodontitis (P), and healthy but reduced periodontium after active periodontal treatment (T) were consecutively enrolled (15 per each group) in the study. A higher number of spots were identified in the proteome of unstimulated whole saliva collected from H and T subjects compared with P group, mainly within the range of 8-40 kDa. Protein spots of interest were analysed by MALDI-TOF-MS, allowing the identification of cystatin SN (CST1) isoform, as confirmed by Western blot. CST1 was markedly expressed in the H group, while it was absent in most P samples (p < 0.001). Interestingly, a distinct CST1 expression was observed in saliva from T patients. CST1 was negatively correlated with the percentage of pathological sites (p < 0.001) and was effective in discriminating active periodontitis from healthy periodontal status (whether H or T). Therefore, salivary CST1 may be a promising non-invasive biomarker for periodontal disease diagnosis and monitoring.

Sonographic features of lymphoma of the major salivary glands diagnosed with ultrasound-guided core needle biopsy in Sjögren's syndrome.

OBJECTIVES: To identify ultrasound (US) features of lymphomas (L) of major salivary glands (SGs) in primary Sjögren's syndrome (pSS) patients and to differentiate US pattern of L and non-L. METHODS: Prospectively, from September 2019 to March 2021, 27 pSS-patients with clinical findings suspicious for L of the SGs underwent US evaluation followed by US-guided core-needle biopsy (CNB). For each patient, we assessed the OMERACT score, dichotomised (0/1 "lower", 2/3 "higher"), and we compared it between L-pSS and nonL-pSS groups. For focal lesions, echogenicity, inner appearance, shape, margins, presence of septa, vascularisation and posterior acoustic features were also assessed and compared between the two groups; we planned to consider as "suspicious" features more frequently associated with L. We expected to compare frequencies at which two or more "suspicious" features were simultaneously present between L-pSS and nonL-pSS. P<0.05 were considered statistically significant. RESULTS: L-pSS showed more inhomogeneous glandular pattern (100% vs. 69.2% higher OMERACT; p=0.0407). For focal lesions, the "suspicious" features identified were: OMERACT grade 3, very hypoechoic, homogenous, oval shape, well-defined margins, presence of septa, colour-Doppler vascularization, posterior acoustic enhancement. 6/8 and 7/8 simultaneous suspicious features were significantly higher among L-pSS patients, compared to nonL-pSS (88.9% vs. 28.6%, p=0.034 for 6/8 features; 77.8% vs. 14.3%, p=0.040 for 7/8 features). CONCLUSIONS: L of the major SGs in pSS was always associated with OMERACT scores 2 or 3 and presented with diffuse or focal patterns. For focal lesions, the association of more "suspicious" features made the diagnosis of L increasingly more likely. This information can help to improve planning of US-guided CNB.

A Generalized Semiempirical Approach to the Modeling of the Optical Band Gap of Ternary Al-(Ga, Nb, Ta, W) Oxides Containing Different Alumina Polymorphs.

A generalization of the modeling equation of optical band gap values for ternary oxides, as a function of cationic ratio composition, is carried out based on the semiempirical correlation between the differences in the electronegativity of oxygen and the average cationic electronegativity proposed some years ago. In this work, a novel approach is suggested to account for the differences in the band gap values of the different polymorphs of binary oxides as well as for ternary oxides existing in different crystalline structures. A preliminary test on the validity of the proposed modeling equations has been carried out by using the numerous experimental data pertaining to alumina and gallia polymorphs as well as the crystalline ternary Ga(1-x)AlxO3 polymorphs (α-Ga(1-x)AlxO3 and ß-Ga(1-x)AlxO3) covering a large range of optical band gap values (4.50-8.50 eV). To make a more rigorous test of the modeling equation, we extended our investigation to amorphous ternary oxides anodically formed on Al-d-metal alloys (Al-Nb, Al-Ta, and Al-W) covering a large range of d-metal composition (xd-metal ≥ 0.2). In the last case, the novel approach allows one to overcome some difficulties experienced in fitting the optical band gap dependence from the Al-d-metal mixed anodic oxide composition as well as to provide a rationale for the departure, at the lowest d-metal content (xd-metal < 0.2), from the behavior observed for anodic films containing higher d-metal content.

Organization Science improves management effectiveness of Marine Protected Areas.

The ecological management effectiveness (EME) of Marine Protected Areas (MPAs) is the degree to which MPAs reach their ecological goals. The significant variability of EME among MPAs has been partly explained by MPA design, management and implementation features (e.g. surface area, enforcement, age of protection). We investigated EME variability by employing, for the first time, Organization Science. Eight Mediterranean MPAs were taken into account as case studies to explore the relationships between EME and MPA features, such as: 1) organizational size (i.e. the ratio between the number of full-time employees and the total MPA surface area), 2) management performance (i.e. the level of effort exerted to enhance and sustain the MPA management, including enforcement), 3) total surface area, and 4) MPA age. The log-response ratios of fish biomass and density in protected vs unprotected (control) areas were used as a proxy of EME. Management performance, organizational size and, to a lesser extent, MPA age were positively correlated with the log-response ratio of fish biomass, whereas total surface area did not display a significant role. None of the four features considered was significantly correlated with the log-response ratio of fish density. Based on our findings, we argue that the employment of Organization Science in the management effectiveness assessment can assist MPA managers to reach MPAs goals more effectively, with a more efficient use of available resources.

Duration and Time Trends in Hospital Stay for Very Preterm Infants Differ Across European Regions.

OBJECTIVES: To compare duration and changes over time in length of hospital stay for very preterm and extremely preterm infants in 10 European regions. DESIGN: Two area-based cohort studies from the same regions in 2003 and 2011/2012. SETTING: Ten regions from nine European countries. PATIENTS: Infants born between 22 + 0 and 31 + 6 weeks of gestational age and surviving to discharge (Models of Organising Access to Intensive Care for Very Preterm Births cohort in 2003, n = 4,011 and Effective Perinatal Intensive Care in Europe cohort in 2011/2012, n = 4,336). INTERVENTIONS: Observational study, no intervention. MEASUREMENTS AND MAIN RESULTS: Maternal and infant characteristics were abstracted from medical records using a common protocol and length of stay until discharge was adjusted for case-mix using negative binomial regression. Mean length of stay was 63.6 days in 2003 and varied from 52.4 to 76.5 days across regions. In 2011/2012, mean length of stay was 63.1 days, with a narrower regional range (54.0-70.1). Low gestational age, small for gestational age, low 5-minute Apgar score, surfactant administration, any surgery, and severe neonatal morbidities increased length of stay. Infant characteristics explained some of the differences between regions and over time, but large variations remained after adjustment. In 2011/2012, mean adjusted length of stay ranged from less than 54 days in the Northern region of the United Kingdom and Wielkopolska, Poland to over 67 days in the Ile-de-France region of France and the Eastern region of the Netherlands. No systematic decrease in very preterm length of stay was observed over time after adjustment for patient case-mix. CONCLUSIONS: A better understanding of the discharge criteria and care practices that contribute to the wide differences in very preterm length of stay across European regions could inform policies to optimize discharge decisions in terms of infant outcomes and health system costs.

Maternal Education Is Associated with Disparities in Breastfeeding at Time of Discharge but Not at Initiation of Enteral Feeding in the Neonatal Intensive Care Unit.

OBJECTIVE: To investigate the relationship between maternal education and breastfeeding in very preterm infants admitted to neonatal intensive care units. STUDY DESIGN: This prospective, population-based cohort study analyzed the data of all very preterm infants admitted to neonatal care during 1 year in 3 regions in Italy (Lazio, Emilia-Romagna, and Marche). The use of mothers' own milk was recorded at initial enteral feedings and at hospital discharge. We used multilevel logistic analysis to model the association between maternal education and breastfeeding outcomes, adjusting for maternal age and country of birth. Region was included as random effect. RESULTS: There were 1047 very preterm infants who received enteral feeding, and 975 were discharged alive. At discharge, the use of mother's own milk, exclusively or not, and feeding directly at the breast were significantly more likely for mothers with an upper secondary education or higher. We found no relationship between maternal education and type of milk at initial enteral feedings. However, the exclusive early use of the mother's own milk at initial feedings was related significantly with receiving any maternal milk and feeding directly at the breast at discharge from hospital, and the association with feeding at the breast was stronger for the least educated mothers. CONCLUSION: In this population-based cohort of very preterm infants, we found a significant and positive association between maternal education and the likelihood of receiving their mother's own milk at the time of discharge. In light of the proven benefits of maternal milk, strategies to support breastfeeding should be targeted to mothers with less education.

Prevalence of parkinsonism estimated using the drug prescription archive: a possible method to estimate the prevalence of a chronic neurological disease?

Many surveys estimated prevalence of parkinsonism, with results varying largely. We used prescription records of medications for parkinsonism to estimate the prevalence of this condition. Retrospective survey based on Lazio (Italy) regional drugs' prescriptions registry. Cases of parkinsonism were defined as those who received a medication for parkinsonism (Dopa and dopa derivatives or Monoamine oxidase B-inhibitors) for at least 6 months in a 5-year period (2005-2009). Crude and standardized prevalence rates at June 2009 were calculated. Crude and standardized prevalence rates of parkinsonism in Lazio were, respectively, 283 per 100,000 (95 % CI 278-287), and 294 per 100,000 (95 % CI 289-298), higher in men than in women (292 per 100,000 vs. 274 per 100,000). The highest overall prevalence rate was observed among people aged 85-89 years (246 per 100,000), while the lowest in subjects aged <65 (38 per 100,000). Prevalence rates in people older than 65 and older 75 were, respectively, 1275 per 100,000 and 1912 per 100,000. Using a regional drug registry, based on currently available health information systems, may be a suitable method to estimate prevalence of parkinsonism, which is essential for public health programming, the more in presence of a demographic shift as the current one.

Modeling of Optical Band-Gap Values of Mixed Oxides Having Spinel Structure AB2O4 (A = Mg, Zn and B = Al, Ga) by a Semiempirical Approach.

Spinel oxides with the general formula AB2O4 comprise a large family of compounds covering a very wide range of band-gap values (1 eV < Eg < 8 eV) as a function of the nature of the metallic cations A and B. Owing to this, the physical properties of these materials have been largely exploited both from a fundamental point of view, for their variable electronic properties, and for their possible use in numerous engineering applications. Herein, the modeling of ZnAl2O4, ZnGa2O4, MgAl2O4, and MgGa2O4 cubic spinel oxides has been carried out by using the semiempirical approach based on the difference of electronegativity between oxygen and the average electronegativity of cations present in the oxides. The results of recent theoretical extensions of our semiempirical approach to ternary and quaternary oxides have been tested for spinel oxides with metallic ions occupying both octahedrally and tetrahedrally coordinated sites in different ratios. A detailed analysis of the experimental band-gap values and comparison with the theoretically estimated values has been carried out for ternary ZnAl2O4, ZnGa2O4, MgAl2O4, and MgGa2O4 spinels as well as for double spinels Mg(Al2xGa2-x)O4 and Zn(Al2xGa2-x)O4, and quaternary mixed oxides (ZnxMg(1-x))Al2O4 and (ZnxMg(1-x))Ga2O4. The wide range of band-gap values reported in the literature for simple or double spinels has been related to the different preparation methods affecting the grain dimension of crystalline spinel samples as well as to the presence of crystallographic defects and/or impurities in the spinel matrix. The good agreement between experimental band-gap values and the theoretical ones strongly supports the use of our semiempirical approach in the area of band-gap engineering of new materials.

Ni,Fe,Co-LDH Coated Porous Transport Layers for Zero-Gap Alkaline Water Electrolyzers.

Next-generation alkaline water electrolyzers will be based on zero-gap configuration to further reduce costs related to technology and to improve performance. Here, anodic porous transport layers (PTLs) for zero-gap alkaline electrolysis are prepared through a facile one-step electrodeposition of Ni,Fe,Co-based layered double hydroxides (LDH) on 304 stainless steel (SS) meshes. Electrodeposited LDH structures are characterized using Scanning Electron Microscopy (SEM) confirming the formation of high surface area catalytic layers. Finally, bi and trimetallic LDH-based PTLs are tested as electrodes for oxygen evolution reaction (OER) in 1 M KOH solution. The best electrodes are based on FeCo LDH, reaching 10 mA cm-2 with an overpotential value of 300 mV. These PTLs are also tested with a chronopotentiometric measurement carried out for 100 h at 50 mA cm-2, showing outstanding durability without signs of electrocatalytic activity degradation.

Efficient Photocatalytic Partial Oxidation of Aromatic Alcohols by Using ZnIn2S4 under Green Conditions.

The ternary chalcogenide ZnIn2S4 (ZIS) has been synthesized by a simple hydrothermal method in which the carcinogen thiacetamide, universally used as a precursor, has been, for the first time, replaced successfully with the harmless thiourea. ZIS has been used as photocatalyst for the partial oxidation of different aromatic alcohols to their corresponding aldehyde in water solution, under ambient conditions and simulated solar light irradiation. The photocatalytic performance of ZnIn2S4 was better than TiO2 P25. In the presence of ZIS for 4-methoxybenzyl alcohol, piperonyl alcohol, and benzyl alcohol, a selectivity towards the corresponding aldehyde of 99% for a conversion of 46%, 75% for a conversion of 81%, and 87% for a conversion of 25%, respectively, was obtained. For the same alcohols a selectivity of 19% for a conversion of 41%, 19% for a conversion of 13%, and 16% for a conversion of 26%, was observed in the presence of TiO2 P25.

Pt-TiO2 catalysts for glycerol photoreforming: comparison of anatase, brookite and rutile polymorphs.

We compared the H2 production from glycerol photoreforming for different TiO2 polymorphs, highlighting an increase of activity in the order Pt-rutile < Pt-P25 ≈ Pt-anatase < Pt-brookite with a different distribution of the reaction intermediates. We show that the highest ability to adsorb water and the different distribution of Pt active sites in brookite can positively influence its photoactivity.

Mono-, bi- and tri-metallic Fe-based platinum group metal-free electrocatalysts derived from phthalocyanine for oxygen reduction reaction in alkaline media.

In this manuscript, a comprehensive study is presented on Fe-based electrocatalysts with mono, bi, and tri-metallic compositions, emphasizing the influence of processing-structure correlations on the electrocatalytic activity for the oxygen reduction reaction (ORR) in the alkaline medium. These electrocatalysts were synthesized through the mixing of transition metal phthalocyanines (TM-Pc) with conductive carbon support, followed by controlled thermal treatment at specific temperatures (600 °C and 900 °C). An extensive analysis was conducted, employing various techniques, including X-ray Absorption Spectroscopy (XAS), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD), providing valuable insights into the structural characteristics of the synthesized nanoparticles. Importantly, an increase in the Fe-Pc weight percentage from 10% to 30% enhanced the ORR activity, although not proportionally. Furthermore, a comparative analysis between mono, bi, and tri-metallic samples subjected to different functionalization temperatures highlighted the superior electrocatalytic activity of electrocatalysts functionalized at 600 °C, particularly Fe 600 and Fe-Ni-Cu 600. These electrocatalysts featured Eon values of 0.96 V vs. RHE and E1/2 values of 0.9 V vs. RHE, with the added benefit of reduced anionic peroxide production. The potential of these Fe-based electrocatalysts to enhance ORR efficiency is underscored by this research, contributing to the development of more effective and sustainable electrocatalysts for energy conversion technologies.

Reviving a Classic Antigen with a Cutting-Edge Approach: Nanobodies for HER2+ Breast Cancer.

The serendipitous discovery of nanobodies (NBs) around two decades ago opened the door to new possibilities for innovative strategies, particularly in cancer treatment. These antigen-binding fragments are derived from heavy-chain-only antibodies naturally found in the serum of camelids and sharks. NBs are an appealing agent for the progress of innovative therapeutic strategies because they combine the advantageous assets of smaller molecules and conventional monoclonal antibodies (mAbs). Moreover, the possibility to produce NBs using bacterial systems reduces manufacturing expenses and speeds up the production process, making them a feasible option for the development of new bio-drugs. Several NBs have been developed over the past 10 years and are currently being tested in clinical trials for various human targets. Here, we provide an overview of the notable structural and biochemical characteristics of NBs, particularly in their application against HER2, an extracellular receptor that often gets aberrantly activated during breast cancer tumorigenesis. The focus is on the recent advancements in diagnostic and therapeutic research up to the present date.

Metformin Protects Rat Skeletal Muscle from Physical Exercise-Induced Injury.

Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy is due to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake and lower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinical applications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism of action on muscle and its effect on muscle performance are unclear. We investigated the effects of Met combined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks while undergoing daily moderate exercise. We evaluated the following: PP through graded endurance exercise test performed before the beginning of the training protocol and 48 h before the end of the training period; blood ALT, AST, LDH and CK-MB levels in order to address muscle damage; and several blood and muscle myokines and the expression of factors believed to be involved in muscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effects of exercise on performance, although it protects myocytes from exercise-induced damage. Moreover, given that Met positively affects exercise-induced muscle adaptation, our data support the idea of the therapeutic application of Met when muscle function and structure are compromised.

The combination of depressive symptoms and smoking shorten life expectancy among the aged.

BACKGROUND: Depression is a potential risk factor for mortality among the aged and it is also associated with other chronic diseases and unhealthy lifestyles that may also affect mortality. The purpose of this study was to investigate the association between depressive symptoms and mortality, controlling for health, nutritional status, and life-style factors. METHODS: A cohort of elderly people (N = 167) was followed-up for ten years. Information on socio-demographic characteristics, medical history, smoking, and alcohol consumption was collected. The primary outcome was all-cause mortality; the secondary outcome was cancer-specific mortality. The Geriatric Depression Scale (GDS-15) was used to assess depression. Using a multivariable Cox proportional hazards regression, we examined the association between depressive symptoms and mortality. RESULTS: Elderly people with depression (scoring above the depression cut-off of 7) had a 53% increased risk of mortality (relative risk (RR) 1.53; 95%CI: 1.05-2.24) compared to non-depressed subjects. The combination of depressive symptoms with smoking was associated with a particularly higher risk of mortality (RR: 2.61; 95%CI: 1.28-5.31), after controlling for potential confounders. CONCLUSIONS: Depressive symptoms are associated with a significantly increased risk of all-cause mortality. The combination of depressive symptoms and smoking shorten life expectancy among the aged.

The Effect of Anodizing Bath Composition on the Electronic Properties of Anodic Ta-Nb Mixed Oxides.

Anodic oxides were grown to 50 V on Ta-Nb sputtering deposited alloys, with high Nb content, in acetate ions containing an aqueous solution to study the effect of the anodizing bath composition on anodic layers' dielectric properties. Photoelectrochemical measurements proved the presence of a photocurrent in the band gap of photon energy lower than oxides, due to optical transitions involving localized electronic states as a consequence of acetate ions incorporation. Flat band potential value estimates assessed the insulating nature of the anodic oxides grown in the acetate buffer solution. Differential capacitance measurements showed that the highest capacitance value was measured for the sample grown on Ta-66%Nb. This capacitance value was higher with respect to those estimated for pure Ta and pure Nb anodic layers and with respect to the same alloy anodized in NaOH solution, i.e., acetate-free anodizing bath.