Biopharmaceutical and nanotoxicological aspects of cyclodextrins for non-invasive topical treatments: A critical review.

Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of their characteristics are low toxicity, biodegradability, and biocompatibility. They are divided into α-, ß-, and γ-cyclodextrins, each with its own particularities. They can undergo surface modifications to improve their performances. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading, and others. Cyclodextrins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles, and suppositories) and allow better topical biological effects of drugs at administration sites such as skin, eyeballs, and oral, nasal, vaginal, and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other administration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles and the in vivo hearing system integrity evaluated to certify that they will be safe and will not cause hearing loss.

Exploiting Polymeric Films as a Multipurpose Drug Delivery System: a Review.

Polymeric films are drug delivery systems that maintain contact with the delivery tissue and sustain a controlled release of therapeutic molecules. These systems allow a longer time of drug contact with the target site in the case of topical treatments and allow the controlled administration of drugs. They can be manufactured by various methods such as solvent casting, hot melt extrusion, electrospinning, and 3D bioprinting. Furthermore, they can employ various polymers, for example PVP, PVA, cellulose derivatives, chitosan, gelling gum, pectin, and alginate. Its versatility is also applicable to different routes of administration, as it can be administered to the skin, oral mucosa, vaginal canal, and eyeballs. All these factors allow numerous combinations to obtain a better treatment. This review focuses on exploring some possible ways to develop them and some particularities and advantages/disadvantages in each case. It also aims to show the versatility of these systems and the advantages and disadvantages in each case, as they bring the opportunity to develop different medicines to facilitate therapies for the most diverse purposes .

Optical Time Reversal from Time-Dependent Epsilon-Near-Zero Media.

Materials with a spatially uniform but temporally varying optical response have applications ranging from magnetic field-free optical isolators to fundamental studies of quantum field theories. However, these effects typically become relevant only for time variations oscillating at optical frequencies, thus presenting a significant hurdle that severely limits the realization of such conditions. Here we present a thin-film material with a permittivity that pulsates (uniformly in space) at optical frequencies and realizes a time-reversing medium of the form originally proposed by Pendry [Science 322, 71 (2008)SCIEAS0036-807510.1126/science.1162087]. We use an optically pumped, 500 nm thick film of epsilon-near-zero (ENZ) material based on Al-doped zinc oxide. An incident probe beam is both negatively refracted and time reversed through a reflected phase-conjugated beam. As a result of the high nonlinearity and the refractive index that is close to zero, the ENZ film leads to time reversed beams (simultaneous negative refraction and phase conjugation) with near-unit efficiency and greater-than-unit internal conversion efficiency. The ENZ platform therefore presents the time-reversal features required, e.g., for efficient subwavelength imaging, all-optical isolators and fundamental quantum field theory studies.

Preserving soft tissue after placing implants in fresh extraction sockets in the maxillary esthetic zone and a prosthetic template for interim crown fabrication: a prospective study.

STATEMENT OF PROBLEM: The technique of immediate implant placement is said to have success rates similar to those of implantation into a healed socket. An implant-supported restoration in an esthetic area must achieve a harmonious balance of functional, esthetic, and biologic imperatives to be considered effective. PURPOSE: The purpose of this clinical study was to assess the height of the interproximal gingival papillae adjacent to immediate implants with immediate loading. The hypothesis was that specific positioning of the proximal contact areas of the interim crowns would facilitate the maintenance or regeneration of the interproximal papilla. MATERIAL AND METHODS: Twenty-eight participants were provided implants (n=36) in the anterior maxillary area that were loaded with a specifically contoured interim crown immediately after tooth extraction. The proximal contact areas of the interim crowns were positioned 5 to 6 mm incisal to the interproximal bony crest by using a prosthetic template. Papilla height was classified according to a previously described papilla index. A comparison was made between the papilla height before the extraction, at interim crown placement after the implant placement, and at 6 and 12 months postoperatively. Parametric and nonparametric tests were used when appropriate (Kolmogorov-Smirnov). Significance was expressed at the α=.05 level. Cross tables were used to describe the changes in the papilla index score. RESULTS: During the 1-year follow-up, the score of the distal and mesial papilla indices increased significantly (repeated-measures Friedman exact test; P=.035 and P=.002). CONCLUSIONS: This prospective study indicated that the use of a prosthetic template for positioning an interim crown on immediately placed implants and for ensuring that the proximal contact areas of the crown with adjacent teeth are 5 to 6 mm incisal to the interproximal bony crest does not seem to hinder the maintenance or regeneration of the height of the interproximal papillae.

The use of a prosthetic template to maintain the papilla in the esthetic zone for immediate implant placement by means of a radiographic procedure.

Implant placement in the esthetic zone requires precise preoperative diagnosis and treatment planning combined with excellent clinical skills. One of the most important factors needed to achieve an optimal esthetic outcome, in addition to the 3-dimensional (3-D) positioning of the dental implant, is to maintain or regenerate the interproximal papilla. This article describes a technique to fabricate a template that includes important aspects of rehabilitation in this area.

Obesity and interpersonal problems: an analysis with the interpersonal circumplex.

UNLABELLED: This study examines the interpersonal problems profiles of obese individuals by cluster analysing the interpersonal problems circumplex scores of participants. The Inventory of Interpersonal Problems-Short Circumplex (IIP-32) was completed by 368 treatment-seeking obese individuals. These data were cluster analysed, and groups of obese subjects defined by varying interpersonal problems were compared with regard to psychological distress, self-esteem, body dissatisfaction, quality of life and binge behaviours. Cluster analyses of the IIP-32 resulted in four clusters, which occupied two quadrants of the interpersonal circumplex. Several differences in body mass index, psychological distress, quality of life and body dissatisfaction emerged across the four interpersonal groups. Although obese individuals reported elevated interpersonal distress, these subjects are not homogeneous with regard to interpersonal problems. Psychiatric co-morbidity and psychological distress may explain these interpersonal differences. These findings underscore the importance for clinicians to assess carefully patients' interpersonal functioning, especially with respect to treatment-seeking obese patients. KEY PRACTITIONER MESSAGE: Research has not consistently specified the types of interpersonal problems most frequently experienced by treatment-seeking obese individuals. Most obese individuals share a friendly-dominant interpersonal style. This research supports the importance of measuring and targeting interpersonal variables in the design and evaluation of obesity treatment programmes.

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice.

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.

Solid Dispersions Incorporated into PVP Films for the Controlled Release of Trans-Resveratrol: Development, Physicochemical and In Vitro Characterizations and In Vivo Cutaneous Anti-Inflammatory Evaluation.

Trans-resveratrol can promote various dermatological effects. However, its high crystallinity decreases its solubility and bioavailability. Therefore, solid dispersions have been developed to promote its amorphization; even so, they present as powders, making cutaneous controlled drug delivery unfeasible and an alternative necessary for their incorporation into other systems. Thus, polyvinylpyrrolidone (PVP) films were chosen with the aim of developing a controlled delivery system to treat inflammation and bacterial infections associated with atopic dermatitis. Four formulations were developed: two with solid dispersions (and trans-resveratrol) and two as controls. The films presented with uniformity, as well as bioadhesive and good barrier properties. X-ray diffraction showed that trans-resveratrol did not recrystallize. Fourier-transform infrared spectroscopy (FT-IR) and thermal analysis evidenced good chemical compatibilities. The in vitro release assay showed release values from 82.27 ± 2.60 to 92.81 ± 2.50% (being a prolonged release). In the in vitro retention assay, trans-resveratrol was retained in the skin, over 24 h, from 42.88 to 53.28%. They also had low cytotoxicity over fibroblasts. The in vivo assay showed a reduction in inflammation up to 66%. The films also avoided Staphylococcus aureus's growth, which worsens atopic dermatitis. According to the results, the developed system is suitable for drug delivery and capable of simultaneously treating inflammation and infections related to atopic dermatitis.

Nanotechnology-based Drug Delivery Systems as Potential for Skin Application: A Review.

Administration of substances through the skin represents a promising alternative, in relation to other drug administration routes, due to its large body surface area, in order to offer ideal and multiple sites for drug administration. In addition, the administration of drugs through the skin avoids the first-pass metabolism, allowing an increase in the bioavailability of drugs, as well as reducing their side effects. However, the stratum corneum (SC) comprises the main barrier of protection against external agents, mainly due to its structure, composition and physicochemical properties, becoming the main limitation for the administration of substances through the skin. In view of the above, pharmaceutical technology has allowed the development of multiple drug delivery systems (DDS), which include liquid crystals (LC), cubosomes, liposomes, polymeric nanoparticles (PNP), nanoemulsions (NE), as well as cyclodextrins (CD) and dendrimers (DND). It appears that the DDS circumvents the problems of drug absorption through the SC layer of the skin, ensuring the release of the drug, as well as optimizing the therapeutic effect locally. This review aims to highlight the DDS that include LC, cubosomes, lipid systems, PNP, as well as CD and DND, to optimize topical skin therapies.

Dynamical Control of Broadband Coherent Absorption in ENZ Films.

Interferometric effects between two counter-propagating beams incident on an optical system can lead to a coherent modulation of the absorption of the total electromagnetic radiation with 100% efficiency even in deeply subwavelength structures. Coherent perfect absorption (CPA) rises from a resonant solution of the scattering matrix and often requires engineered optical properties. For instance, thin film CPA benefits from complex nanostructures with suitable resonance, albeit at a loss of operational bandwidth. In this work, we theoretically and experimentally demonstrate a broadband CPA based on light-with-light modulation in epsilon-near-zero (ENZ) subwavelength films. We show that unpatterned ENZ films with different thicknesses exhibit broadband CPA with a near-unity maximum value located at the ENZ wavelength. By using Kerr optical nonlinearities, we dynamically tune the visibility and peak wavelength of the total energy modulation. Our results based on homogeneous thick ENZ media open a route towards on-chip devices that require efficient light absorption and dynamical tunability.

Characteristics, Biological Properties and Analytical Methods of Trans-Resveratrol: A Review.

Trans-resveratrol (TR) is the biological active isomer of resveratrol and the one responsible for therapeutic effects; both molecules are non-flavonoid phenolics of the stilbenes class found mainly in berries and red grapes. TR biological properties lie in modulation of various enzymatic classes. It is a promising candidate to novel drugs due its applications in pharmaceutical and cosmetic industries, such as anticarcinogenic, antidiabetic, antiacne, antioxidant, anti-inflammatory, neuroprotective, and photoprotector agent. It has effects on bone metabolism, gastrointestinal tract, eyes, kidneys, and in obesity treatment as well. Nevertheless, its low solubility in water and other polar solvents may be a hindrance to its therapeutic effects. Various strategies been developed to overcome these issues, such as the drug delivery systems. The present study performed a research about methods to identify TR and RESV in several samples (raw materials, wines, food supplements, drug delivery systems, and blood plasma). Most of the studies tend to analyze TR and RESV by high performance liquid chromatography (HPLC) coupled with different detectors, even so, there are reports of the use of capillary electrophoresis, electron spin resonance, gas chromatography, near-infrared luminescence, UV-Vis spectrophotometer, and vibrational spectrophotometry, for this purpose. Thus, the review evaluates the biological activity of TR and demonstrates the currently used analytical methods for its quantification in different matrices.

Peri-implant Soft Tissue Management: Cairo Opinion Consensus Conference.

Peri-implant soft tissues play a role of paramount importance, not only on the esthetic appearance, but also on the maintenance and long-term stability of implants. The present report presents the conclusions from the Consensus Conference of the South European North African Middle Eastern Implantology & Modern Dentistry Association (SENAME) (4-6 November 2016, Cairo, Egypt). The conference focused on the topic of the soft tissue around dental implants, and in particular, on the influence of implant configurations on the marginal soft tissues, soft tissue alterations after immediate, early or delayed implant placement and immediate loading, the long-term outcomes of soft tissue stability around dental implants, and soft tissue augmentation around dental implants. Thirty world experts in this field were invited to take part in this two-day event; however, only 29 experts were in the final consensus voting process.

[Human risk factors and injuries due to road accidents: analysis of current data]. / Fattori di rischio umani e infortuni conseguenti agli incidenti stradali: analisi di dati correnti.

OBJECTIVES: several studies have shown that most road accidents are due to human factors, and that these are strongly linked to a drive's age and sex. The aim of this study is to test the role that some human factors play in road accidents by analysing current road accident data in the Province of Pavia, in Northern Italy. DESIGN: road accidents that occurred in 2004 were analysed by integrating the paper database of the vehicle licensing office, properly computerised, with the 911 database of the Province of Pavia. This study has been carried out by analysing 1.347 road accidents and the associated 2.908 drivers of motorised vehicles. SETTING: Northern Italy, the Province of Pavia. RESULTS: the death rate of drivers of 2-wheeled vehicles is almost nine times higher than that of 4-wheeled vehicles. Analysis shows that females are twice as exposed to road accidents than males; it also shows the benefits of extensive road education training and of being aged 30-64 and older. Drivers who have already been punished and have had their driving license scores reduced are likely to respond rapidly when in a dangerous situation and also to be without blame after an accident. Motorcycle riders are 25 times more likely to suffer serious injury than drivers of cars. Additionally, the risk of a woman being seriously injured is higher than for a man. CONCLUSION: females, young drivers and motorcycle riders who have not previously been penalised for a previous traffic violation have a higher risk of being seriously injured; females and motorcycle riders are also at greater risk of being seriously injured. We hope that this analysis will be used to improve preventative interventions for road accidents.r.

Severity of irritable bowel syndrome in patients with temporomandibular disorders: A case-control study.

BACKGROUND: To assess the risk and severity of IBS in a population of TMD patients. MATERIAL AND METHODS: Subjects for the study group were recruited from patients attending the Dental Clinic. Health controls (HC) were recruited among patients' friends and clinic staff. All subjects filled in the RDC/TMD questionnaire and the ROME III questionnaire for the diagnosis of IBS. The IBS Severity Scoring System (IBS-SSS) was used to evaluate the severity of each case of IBS. Categorical variables were compared through the Chi square test. The risk of having abdominal pain was analysed using logistic regression. RESULTS: Twenty-two (46.8%) cases of IBS were diagnosed among TMD patients, whereas only 4 (11.4%) were in the HC group. This difference was statistically significant (χ2(1)=11.6; p<.01). The differences in the distribution of IBS-SSS were statistically significant (χ2(3)=12.49; p<.05). The regression model resulted statistically significant (χ2(5)=24.08; p<.001, R2=.37): abdominal pain was significantly related to nonspecific physical symptoms independent of the other variables. CONCLUSIONS: TMD patients had a greater risk of having IBS compared to HC. TMD patients presented also more severe form of IBS than HC. Key words:Temporomandibular disorders, irritable bowel syndrome, facial pain, case-control study.

Clinical Relevance of Bone Density Values from CT Related to Dental Implant Stability: A Retrospective Study.

PURPOSE: The majority of the techniques used to assess the primary implant stability are subjective and empirical and can be used during or after the surgery. The aim of this study is to evaluate the bone density prior to surgery, in order to give recommendations to the clinician about the best surgical technique and the type of implant which is needed. MATERIALS AND METHODS: A surgeon operated on 75 patients for 269 implants over the period 2010-2014. He required a CT to plan the surgery and he documented the type, the diameters, and the lengths of the implants, the insertion torque, and the ISQ values. At a later stage another clinician measured bone density and cortical thickness. We endeavoured to get the most accurate superimposition between the implants placed by the surgeon and those placed by the clinician. RESULTS: In maxilla ISQ showed a significant positive correlation with HU values detected for coronal-buccal (r = 0.302; p = 0.020) and middle-lingual (r = 0.295; p = 0.023). Torque showed a positive correlation with cortical bone thickness at the middle of the ridge (ρ = 0.196; p = 0.032). CONCLUSION: It is important to take into consideration the Hounsfield Units and the cortical thickness as predictive parameters during the preoperative assessment, with regard to the choice of the implant type as well as the surgical technique.

High risk of temporomandibular disorder in irritable bowel syndrome: Is there a correlation with greater illness severity?

AIM: To investigate the prevalence and the risk of temporomandibular disorders (TMDs) in patients with irritable bowel syndrome (IBS) (including each subtype: constipation, diarrhoea, and mixed) compared to the general population. METHODS: Between January 2014 and December 2015 we enrolled consecutively adult patients diagnosed with IBS at the outpatient clinic of the University of Salerno and healthy controls (HC) without IBS. At enrollment, we analyzed all patients for the presence of TMDs according to the Research Diagnostic Criteria for TMD. RESULTS: We enrolled 91 IBS patients (23 IBS-D, 30 IBS-C and 38 IBS-M) and 57 HC in the study. We found a higher risk of having TMD (OR = 3.41, 95%CI: 1.66-7.01) compared to the HC. The risk of having TMD was independent of IBS-subtype. Multiple regression analysis showed that facial pain was positively related to abdominal pain and higher level of depression. CONCLUSION: IBS patients had a more than three times greater risk of TMD compared to HC. The risk of having TMD was similar in different IBS subtypes. IBS patients that also fulfilled criteria for TMD seem to share along with chronic facial and abdominal pain a significant co-occurrence with psychiatric disorders and female preponderance.

Dental erosion in patients seeking treatment for gastrointestinal complaints: a case series.

INTRODUCTION: Eating disorders which embrace anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified can be life-threatening due to general medical complications; however, the diagnosis of eating disorder is often delayed due to a low suspicion index. Gastroenterologists are health care providers who may come into contact with patients with undiagnosed eating disorders; it has been previously demonstrated that patients with eating disorders frequently have a significant association with functional dyspepsia. Signs of dental erosion have been described in patients with eating disorders; hence, they may help to identify eating disorders in patients who present with functional dyspepsia and deny having an eating disorder. CASE PRESENTATION: In this report we describe three cases (a 25-year-old white woman, a 24-year-old white woman, and a 40-year-old white man) with undiagnosed eating disorders, in which a more comprehensive approach, such as the recognition of dental erosion joined with a careful gastrointestinal investigation, was performed to reach a final diagnosis of an eating disorder. CONCLUSIONS: The screening for dental erosion in patients seeking or receiving medical treatment for dyspeptic symptoms in a gastrointestinal out-patient clinic could be an aid for gastroenterologists to recognize the presence of an underlying eating disorder. A close collaboration with dentists, in addition to psychiatrists, could provide a more favorable treatment outcome.

Short implants as an alternative to crestal sinus lift: A 1-year multicentre randomised controlled trial.

PURPOSE: To evaluate the efficacy of short (5 or 6 mm-long) dental implants versus 10 mm or longer implants placed in crestally-lifted sinuses. MATERIALS AND METHODS: Twenty partially edentulous patients having 5 to 7 mm of residual crestal height and at least 7 mm thickness below the maxillary sinuses as measured on computerised tomography scans were randomised according to a parallel group design to receive either one to two 5 or 6 mm-long implants (10 patients) or 10 mm-long implants (10 patients) after crestal sinus lifting and grafting with anorganic bovine bone (Endobon). Implants were left to heal submerged for 4 months and loaded with reinforced acrylic provisional prostheses, and then replaced after 4 months, by definitive provisionally cemented or screw-retained metal-ceramic or metal-resin prostheses. Outcome measures were prosthesis and implant failures, any complications, radiographic peri-implant marginal bone level changes and patient's satisfaction assessed by blinded assessors, when possible. All patients were followed up to 1 year after loading. RESULTS: No patient dropped out, no failures or complications occurred. Short implants lost 0.70 ± 0.19 mm of peri-implant marginal bone and long implants lost 0.87 ± 0.21 mm of periimplant marginal bone 1 year after loading, the difference between the two groups showing no statistical significance (difference = -0.17 mm; 95% CI: -0.35 to 0.02; P = 0.078). CONCLUSIONS: Both techniques achieved excellent results and no differences were observed between prostheses supported by one to two implants, 5 to 6 mm-long or 10 mm-long in the posterior atrophic maxillae up to 1-year after loading, therefore it is up to the clinicians to decide which procedure to use, although longer follow-ups are needed to understand if one of these procedures could be more effective in the long-term.

Binge eating partially mediates the relationship between body image dissatisfaction and psychological distress in obese treatment seeking individuals.

INTRODUCTION: We compared the binge eating pathway linking body image dissatisfaction (BID) and psychological distress of obese adults entering and not entering psychological treatment for their weight problems. METHOD: 90 obese participants seeking an integrated treatment (OB-IT) and 87 obese participants seeking only medical treatment (OB-MT) for their weight problems completed questionnaires on BID, binge eating and psychological well-being. RESULTS: Only in the OB-IT group, binge eating behaviors mediated the relationship between BID and psychological distress. CONCLUSIONS: Both BID and binge eating behaviors need to be addressed in the psychological and medical treatment for obesity to enhance psychological well-being.

Computer guided implantology accuracy and complications.

The computer-based method allows the computerized planning of a surgical implantology procedure, using computed tomography (CT) of the maxillary bones and prosthesis. This procedure, however, is not error-free, unless the operator has been well trained and strictly follows the protocol. A 70-year-old woman whom was edentulous asked for a lower jaw implant-supported prosthesis. A computer-guided surgery was planned with an immediate loading according to the NobelGuide technique. However, prior to surgery, new dentures were constructed to adjust the vertical dimension. An interim screwed metal-resin prosthesis was delivered just after the surgery; however, after only two weeks, it was removed because of a complication. Finally, a screwed implant bridge was delivered. The computer guided surgery is a useful procedure when based on an accurate 3D CT-based image data and an implant planning software which minimizes errors.