Gut Microbiota Are a Novel Source of Biomarkers for Immunotherapy in Non-Small-Cell Lung Cancer (NSCLC).

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small-Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies on a variety of factors which may allow for the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the microbiota. The latter is made by all the bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying the gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all the conditions influencing the gut microbiota and, therefore, affecting the response to immunotherapy, iRAEs, and their management in NSCLC patients. The investigation of the landscape of these biological events can allow for novel insights into the optimal management of NSCLC immunotherapy.

The impact of PARP inhibitors in the whole scenario of ovarian cancer management: A systematic review and network meta-analysis.

BACKGROUND: Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived agents remains the major predictor of long-term outcomes. PATIENT AND METHODS: We aimed to identify the best treatment of the aEOC in terms of efficacy and safety, considering all treatment phases. A systematic literature search has been done to compare all treatments in aEOC population. Randomized trials with available survival and safety data published in the 2011-2022 timeframe were enclosed. Only trials reporting the BRCA or HRD (Homologous Recombination Deficiency) status were considered. DATA EXTRACTION AND SYNTHESIS: A ranking of treatment schedules on the progression-free survival (PFS) endpoint was performed. The random-effect model was used to elaborate and extract data. The Network Meta-Analysis (NMA) by Bayesian model was performed by STATA v17. Data on PFS were extracted in terms of Hazard ratio with relative confidence intervals. RESULTS: This NMA involved 18 trials for a total of 9105 patients. Within 12 treatment groups, we performed 3 different sensitivity analyses including "all comers" Intention to Treat (ITT) population, BRCA-mutated (BRCAm), and HRD subgroups, respectively. Considering the SUCRA-reported cumulative PFS probabilities, we showed that in the ITT population, the inferred best treatment was niraparib plus bevacizumab with a SUCRA of 96.7. In the BRCAm subgroup, the best SUCRA was for olaparib plus chemotherapy (96,9). The HRD population showed an inferred best treatment for niraparib plus bevacizumab (SUCRA 98,4). Moreover, we reported a cumulative summary of PARPi toxicity, in which different 3-4 grade toxicity profiles were observed, despite the PARPi "class effect" in terms of efficacy. CONCLUSIONS: Considering all aEOC subgroups, the best therapeutical option was identified as PARPi plus chemotherapy and/or antiangiogenetic agents, suggesting the relevance of combinatory approaches based on molecular profile. This work underlines the potential value of "chemo-free" regimens to prolong the platinum-free interval (PFI).

Child-therapist and parent-therapist alliances and outcome in the treatment of children with oppositional defiant/conduct disorder.

OBJECTIVE: This study examined the quality of therapeutic alliance from different rater perspectives (child, parent, therapist) in cognitive behavioural therapy for children with oppositional defiant disorder (ODD) and conduct disorder (CD), and its association with symptom severity. Further, a panel model with an autoregressive cross-lagged panel design was used to explore whether therapist-rated and parent-rated therapeutic alliance influences change in symptom severity, or vice versa. METHODS: Sixty boys aged 6-12 years with a principal diagnosis of ODD/CD, and their parents, received individually delivered social competence training for childhood aggressive behaviour problems. Child, therapist, and parent ratings of therapeutic alliance and symptom severity were measured twice. RESULTS: Our results indicate good to very good therapeutic alliance that was relatively stable over time. The cross-sectional analyses of the alliance-symptom association revealed moderate correlations. However, effects of early alliance on later treatment outcome or of early symptom severity on later alliance were marginal. The only significant association was found between early parent-rated therapist-parent alliance and later parent-rated symptom severity. CONCLUSION: Our study shows a moderate correlation between simultaneously assessed therapeutic alliance and symptoms. The findings of the panel model indicate that an early good therapeutic alliance is a component of later therapeutic success (parent perspective).

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy.

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027). Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation.

Reaping the Benefits of Microorganisms in Cropping Systems: Is the Regulatory Policy Adequate?

Within food plant cropping systems, microorganisms provide vital functions and ecosystem services, such as biological pest and disease control, promotion of plant growth and crop quality, and biodegradation of organic matter and pollutants. The beneficial effects of microorganisms can be achieved and/or enhanced by agricultural management measures that target the resident microbial biodiversity or by augmentation with domesticated and propagated microbial strains. This study presents a critical review of the current legislation and regulatory policies pertaining to the utilization of plant-beneficial microorganisms in the European Union (EU). For augmentative approaches, the nature of the intended effect and the product claim determine how a microbiological product is categorized and regulated, and pre-market authorization may be mandatory. Typically, microbial products have been incorporated into frameworks that were designed for evaluating non-living substances, and are therefore not well suited to the specific properties of live microorganisms. We suggest that regulatory harmonization across the sector could stimulate technical development and facilitate implementation of crop management methods employing microorganisms. Possible scenarios for regulatory reform in the longer term are discussed, but more investigation into their feasibility is needed. The findings of this study should serve as a catalyst for more efficient future use of plant-beneficial microorganisms, to the benefit of agriculture as well as the environment.

Why Do Consumers Intend to Purchase Natural Food? Integrating Theory of Planned Behavior, Value-Belief-Norm Theory, and Trust.

Natural labels are increasingly present in the market and appreciated by consumers, despite formal regulation still missing. Knowing the psychosocial factors that may predict natural food choice may be useful to understand what drives consumers to choose this category of food. We analyzed the antecedents of consumers' intention to purchase natural food, testing a theoretical model that integrates the theory of planned behavior (TPB), the value-belief-norm (VBN) theory, and consumers' trust in natural food. A sample of Italian participants (N = 1018) filled an online questionnaire assessing intention to buy natural food, TPB and VBN variables, and trust in the natural food supply chain. The model applied yielded results which confirmed the predictiveness of the tested integrated model. Attitude and perceived behavioral control were the strongest antecedents of intention, followed by trust and personal norm. Consumers' intention to buy natural food was also associated with their evaluation of the consequences and possibilities related to the purchase behavior, as well as with their moral evaluation attributable to pro-environmental determinants.

Do consumers understand health claims on extra-virgin olive oil?

Health claims have been introduced in food labelling to support consumers' awareness of healthy food choices and to enhance a healthy diet. Even though many countries around the world have developed legislation and guidelines to regulate the introduction of health claims on food labels, there is the evidence that many consumers do not understand the meaning of these claims. This study analyses whether Italian consumers really understand authorized health claims on extra-virgin olive oil and what are the drivers of such understanding. An Olive Oil Health Claims Understanding index was constructed and embedded in a structured questionnaire, which was then administered to a representative sample of Italian household members who are responsible for food shopping (N = 1,030). Results from the survey showed that only 36% of the respondents understood the meaning of the authorized health claims on extra-virgin olive oil. Moreover, the findings confirmed that the understanding of health claims is related to socio-demographic, personal and psychographic characteristics of consumers, as well as to their attitudes toward using food as medicine. Outcomes also proved the central role of nutrition knowledge in affecting understanding of health claims.

Dimensions of Autistic Traits Rated by Parents of Children and Adolescents with Suspected Autism Spectrum Disorders.

To examine the factor structure of autism spectrum disorder (ASD) and the psychometric properties of the German Symptom Checklist for Autism Spectrum Disorders (SCL-ASD). Data were collected from 312 clinical referrals with suspected ASD (2-18 years). Confirmatory factor analyses and analyses of reliability, convergent and divergent validity were performed. A bifactor model with one general ASD factor and two specific factors (interaction-communication; restricted, repetitive behaviors) provided an adequate data fit. Internal consistencies of the SCL-ASD subscales and the total scale were > .70. Correlations with measures of ASD traits were higher than correlations with measures of externalizing and internalizing symptoms. The results support a factor structure consistent with DSM-5/ICD-11 criteria. The SCL-ASD has sound psychometric properties.

Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade.

BACKGROUND: Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients. METHODS: We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients' outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing. RESULTS: A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1. CONCLUSIONS: This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.

Cross-Cultural Validity of the Child and Adolescent Dispositions Model in a Clinical Sample of Children With Externalizing Behavior Problems.

Background: The Child and Adolescent Dispositions Scale-parent rating (CADS-P) explores three emotional dispositions that may enlarge the probability of future externalizing problem behavior. The English version has proven its psychometric quality within a population-based sample of children and adolescents. The presents study investigates the German version of the CADS-P by examining a clinically referred sample of children with externalizing behavior problems. Methods:The sample included 132 children aged 4-11 years with a diagnosis of attention- deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD). The factor structure of the CADS-P was evaluated using exploratory (EFA) and confirmatory factor analyses (CFA). Reliability was estimated using internal consistency (Cronbach's alpha). Validity was assessed through linear regression analyses, with symptoms of externalizing [conduct disorder (CD), ODD, ADHD] and internalizing behavior problems (anxiety, depression) as criterion variables and the three CADS-P factor scores as predictors. Results:After eliminating eight items due to insufficient psychometric properties, EFA and CFA supported a three-factor solution for the German CADS-P. Cronbach's alpha coefficient exceeded α = 0.70 for all subscales. Mostly, as predicted, the CADS-P dimensions were associated with symptoms of ODD/CD and ADHD and symptoms of anxiety and depression. Conclusions:The present study provides evidence for the cross-cultural validity of the CADS- P in a non-English-Speaking country. Results show that the German version of the CADS-P is a reliable and valid parent questionnaire for assessing prosociality, negative emotionality and daring as emotional dispositions that may enlarge the probability to develop externalizing problem behavior. Trial Registration: The study was approved by the review board of the Medical Faculty of the University of Cologne (ID 09-123) and was pre-registered at ClinicalTrials.gov (ID: NCT01350986).

Early blood rise in auto-antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic-non-small cell lung cancer patients treated with PD-1 immune-check point blockade by nivolumab.

Immune-checkpoint blockade by Nivolumab, a human monoclonal antibody to programmed cell death receptor-1, is an emerging treatment for metastatic non-small cell lung cancer (mNSCLC). In order to prolong patient survival, this treatment requires a continuous cross-priming of tumor derived-antigens to supply fresh tumor-specific immune-effectors; a phenomenon that may also trigger auto-immune-related adverse events (irAEs). The present study therefore investigated the prognostic value of multiple autoimmunity-associated parameters in patients with mNSCLC who were undergoing Nivolumab treatment. This retrospective study included 92 mNSCLC patients who received salvage therapy with Nivolumab (3 mg/kg, biweekly) between September 2015 and June 2018. Log-rank test, Mantel-Cox and McPherson analyses were conducted to correlate patient progression-free survival (PFS) and overall survival (OS) with different parameters including blood cell counts, serum inflammatory markers and auto-antibodies (AAbs). A median PFS and OS of 10 [inter-quartile range (IQR): 5.8-14.2] and 16 [IQR: 6.2-25.8] months, respectively, were recorded, which did not correlated with age, histology or the number of previous chemotherapy lines. Male gender, the type of therapeutic regimens received prior to Nivolumab, and the occurrence of irAEs were revealed to be positive predictors of prolonged survival (P<0.05). Early detection (within 30 days) of >1AAbs among anti-nuclear antigens (ANAs), extractable nuclear antigens (ENAs) and anti-smooth cell antigens (ASMAs) correlated with prolonged PFS [hazard ratio (HR)=0.23; 95% confidence interval (CI): 0.08-0.62; P=0.004] and OS [HR=0.28 (95% CI: 0.09-0.88), P=0.03], with the type of treatment received prior to nivolumab (P=0.007) and with the risk of irAEs (P=0.002). In conclusion, increased serum levels of ANA, ENA and/or ASMA are consequential to Nivolumab administration and are predictive of a positive outcome in mNSCLC patients.

Consumers' Perceptions and Preferences for Bitterness in Vegetable Foods: The Case of Extra-Virgin Olive Oil and Brassicaceae-A Narrative Review.

The presence of some healthy phytochemicals in food can be paired with high bitterness, and consumers have a widespread avoidance toward bitter-tasting food. This causes a gap between preferences and healthy needs of consumers. Therefore, this review collected insights from literature belonging to different discipline domains in order to have a broad view of the current state-of-the-art about biochemical aspects and consumers' perceptions and preferences toward foods with an enhanced bitter taste. In detail, we focused on two core products of the Mediterranean diet: Extra-virgin olive oil (EVOO) and Brassicaceae, both characterized by specific phytochemicals having strong healthy properties and bitter-pungent taste. Results suggested that, although bitter taste is a general driver of dislike, some exceptions can be represented by: niches of consumers (e.g., innovators and organic buyers), foods consumed with specific purposes (e.g., coffee, chocolate, and alcoholic beverages). The level of bitterness perceived by the consumers can be modulated through exposure, information on benefits, and elements within the environment (e.g., music). Thus, these insights can be used to develop specific campaigns aimed at promoting bitter (healthy) food, considering also the key role that could be played by food pairings.

Are (All) Consumers Averse to Bitter Taste?

The current study combined hedonic liking with non-hypothetical experimental auctions to measure consumer preferences for bitter tasting food and identify individual socio-demographic and psychographic characteristics that influence bitter aversion. Furthermore, the research analyzed whether consumer preferences for bitter food were influenced by sensory and health-related information. Findings reveal that respondents (N = 205) are not averse to bitter taste; while, socio-demographic traits influence bitter acceptance, as higher education level and gender (female) positively affect preferences, together with specific individual characteristics as high compensatory health beliefs. Moreover, results prove that participants positively respond to health-related information, whereas information on bitterness-taste generates lower preferences.

The Era of PARP inhibitors in ovarian cancer: "Class Action" or not? A systematic review and meta-analysis.

INTRODUCTION: Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. PATIENTS AND METHODS: Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings. We considered the January 2008 - April 2018 time frame. Progression free survival (PFS) was the primary end-point, toxicities were secondary end-points. Hazard ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3-4 toxicity rates, were extracted from retrieved studies and included in the current analysis. Meta-analysis was carried out by the fixed and random effect models. We conducted this meta-analysis to also compare indirectly the efficacy of different PARPis in EOC patients. RESULTS: Five randomized trials for a total of 1839 patients were selected and included in the final analysis. In particular, we evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), respectively. Regarding safety profile, no significant differences were detected in all grade toxicities, however, taking into account 3-4 grade toxicities and SAEs (severe adverse events), we show that rucaparib-treated patients reported major abdominal pain events, while niraparib-treated patients were associated with the highest percentage of haematological toxicities, hypothesizing a drug effect for the safety analysis. In the indirect comparisons, significant differences were not detected on PFS for the different agents. CONCLUSIONS: We confirm a significant benefit in survival outcome of PARPis for EOC patients with a "class effect" on the bases of narrow CI and indirect comparisons in the different groups. Therefore, we underline that this strategy is of special value in BRCA-mutated patients because genetic testing allows best patient selection for all PARPis with the added value of individualized prevention in familiars.

Consumers' willingness to buy innovative traditional food products: The case of extra-virgin olive oil extracted by ultrasound.

Innovation is fundamental for all agri-food companies to increase competitiveness, however the industrial process of extra virgin olive oil (EVOO) has changed very little over the last few decades. As it is a traditional food product (TFP), the main obstacle to innovation is precisely its traditional nature. According to the literature, any innovation regarding TFPs should be considered in terms of the specific product, and market success mainly depends upon the perceptions and traits of consumers. The present study evaluated the willingness of consumers to buy an innovative EVOO obtained by ultrasound extraction (ultrasonic EVOO) through an ordered logit model. The sample was composed by 961 EVOO consumers. The average age of respondents was 39 and the majority were female (55.4%). At first, the respondents reacted almost equally to the idea of buying ultrasonic EVOO, with 49% of the sample stating they were not willing to buy the product and 51% stating that they were willing to. The major insight from our study is that consumers who are the most willing to buy the product are those who formed a positive quality perception after being introduced to the key characteristics of the new product. In addition, the willingness to buy seems to be higher for consumers who prefer EVOO with a fruity flavour and without a sweet taste, for consumers who attach great importance to the taste of food and with a higher than average educational level. This predominant role of consumers' perception in the case of innovative TFPs should, thus, be researched further.

Extra-virgin olive oil: are consumers provided with the sensory quality they want? A hedonic price model with sensory attributes.

BACKGROUND: Over the years, niche-differentiation strategies and food policies have pushed quality standards of European extra-virgin olive oil towards a product that has a sensory profile consisting of fruity, bitter and pungent notes, with such oils having excellent healthy features. However, it is unclear whether typical consumers are ready for a richer and more complex sensory profile than the neutral one historically found on the market. This potential discrepancy is investigated in the present study aiiming to determine whether current demand is able to appreciate this path of quality enhancement. Implicit prices for each and every attribute of extra-virgin olive oil with a focus on sensory characteristics were investigated using a hedonic price model. RESULTS: Although confirming the importance of origin and terroir for extra-virgin olive oil, the results of the present study strongly confirm the discrepancy between what is currently valued on the market and what novel supply trends are trying to achieve in terms of the sensory properties of such products. CONCLUSION: Increasing consumer awareness about the direct link between the health quality of oils and their sensory profile appears to be necessary to make quality enhancement programs more successful on the market and hence more effective for companies. © 2017 Society of Chemical Industry.

New Trends in the Chinese Diet: Cultural Influences on Consumer Behaviour.

China is one of the most dynamic regions in the world in terms of economic growth and development. Such development has inevitably influenced the structure and habits of Chinese society. Whilst the economic condition of the middle class and high-income segment has steadily improved, cultural changes are also under way: ancient Chinese traditions now include major elements from other cultures, most notably the West. The above scenario is the background to this paper. A structured research-administered survey was developed to investigate the changes in the Chinese consumer food culture: 500 urban participants were randomly selected from six reference cities, covering geographically almost the whole country. This study aims not only to analyze the propensity of consumers to include food products from other countries in their ancient Chinese culinary culture, but also represents an initial attempt to perform a market segmentation of Chinese consumers according to their degree of cultural openness towards non-Chinese food, taking into account socio-demographic, cognitive and psychographic variables.

The effect of communication and implicit associations on consuming insects: An experiment in Denmark and Italy.

It has been widely noted that the introduction of insects in Westerns' diet might be a promising path towards a more sustainable food consumption. However, Westerns' are almost disgusted and sceptical about the eating of insects. In the current paper we report the results of an experiment conducted in two European countries-Denmark and Italy-different for food culture and familiarity with the topic of eating insects. We investigated the possibility to foster people's willingness to eat insect-based food through communication, also comparing messages based on individual vs. societal benefits of the eating of insects. Communication proved to be effective on intention and behaviour, and the societal message appeared to be more robust over time. The communication effect is significant across nation, gender, and previous knowledge about the topic. In addition, we investigated the impact of non-conscious negative associations with insects on the choice to eat vs. not eat insect-based food. Implicit attitudes proved to be a powerful factor in relation to behaviour, yet they did not impede the effectiveness of communication.

Effectiveness of a diode laser in addition to non-surgical periodontal therapy: study of intervention.

BACKGROUND: Chronic periodontitis affects 47% of adult population over the age of 30. The first phase of periodontal treatment is always represented by scaling and root planning (SRP), that is a causal, non-surgical therapy that recognizes as primary aims the control of bacterial infection and the reduction of periodontal plaque-associated inflammation. Yet, another innovative causal therapy is represented by the irradiation of periodontal pockets with laser. AIM: To evaluate the effect of a 940-nm diode laser as an adjunct to SRP in patients affected by periodontitis. MATERIALS AND METHODS: Sixty-eight adult patients with moderate-to-severe periodontitis were sequentially enrolled and undergone to periodontal examination (V1) in order to detect gingival index (GI), plaque index (PI) and probing depth (PD). The patients were randomly divided into two groups: the first (n=34) received SRP treatment alone, the control group (n=34) received SRP and 940-nm diode laser therapy. RESULTS: Data were analyzed by Student's t-test, with two tails; for all clinical parameters, both groups reported statistically significant differences compared to basal values (p<0.0001). Both procedures were effective in improving GI, PI and PD, but the use of diode laser was associated with more evident results. CONCLUSIONS: Considered the better clinical outcomes, diode laser can be routinely associated with SRP in the treatment of periodontal pockets of patients with moderate-to-severe periodontitis.

miR-29b negatively regulates human osteoclastic cell differentiation and function: implications for the treatment of multiple myeloma-related bone disease.

Skeletal homeostasis relies upon a fine tuning of osteoclast (OCL)-mediated bone resorption and osteoblast (OBL)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease (BD). Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells, significantly impairs tartrate acid phosphatase (TRAcP) expression, lacunae generation, and collagen degradation, which are relevant hallmarks of OCL activity. Accordingly, expression of cathepsin K and metalloproteinase 9 (MMP9) as well as actin ring rearrangement were impaired in the presence of miR-29b. Moreover, we found that canonical targets C-FOS and metalloproteinase 2 are suppressed by constitutive miR-29b expression which also downregulated the master OCL transcription factor, NAFTc-1. Overall, these data indicate that enforced expression of miR-29b impairs OCL differentiation and overcomes OCL activation triggered by MM cells, providing a rationale for miR-29b-based treatment of MM-related BD.