The endogenous oxytocin after manipulative osteopathic treatment in full-term pregnant women.

OBJECTIVE: The aim of this study is to assess whether the touch of osteopathic manipulative treatment (OMT) can affect the endogenous production of oxytocin in full-term pregnant women and the assessment of well-being following the treatment. PATIENTS AND METHODS: In this study have been enrolled 57 pregnant women at full-term pregnancy (37th-41st week) for evaluation of the concentration of salivary oxytocin 2 minutes before and 2 minutes after a single session of OMT by an osteopath lasting for 30 minutes. Pre-OMT and post-OMT saliva samples were collected with the use of Salivette® salivary swabs. 7 salivary swabs were excluded from the analysis. 50 samples were analyzed with an appropriate ELISA kit. RESULTS: The mean OT salivary concentration pre-OMT was 89.98±16.39, and post-OMT was 100.60±19.13 tends to increase with p=0.0000051. In multivariate analysis, two subgroups show interesting data in the mean difference in OT salivary concentration post-OMT: women with painful contractions (p=0.06) and women under 35 years (p=0.09). CONCLUSIONS: The results of this study demonstrate that the effectiveness of OMT-increasing endogenous oxytocin is statistically significant in full-term pregnant women. The sensation of well-being found in most women indicates that there has been a predominantly central rather than peripheral oxytocin release after OMT.

First and second branchial arch involvement in mandibulofacial dysostosis Guion-Almeida type.

BACKGROUND: Mandibulofacial dysostosis Guion-Almeida Type (MFDGA; OMIM#610536) is a rare autosomal dominant genetic disorder caused by heterozygous pathogenic variants in the EFTUD2 gene. Mandibulofacial dysostoses are characterised by the core triad malar hypoplasia, maxillary hypoplasia and dysplastic ears, all derived by the impaired development of the first and second branchial arches. Differential diagnosis is often challenging. The early genetic diagnosis is extremely useful, not only for the correct management of cranial malformations, but also for the early diagnosis and treatment of the comorbidities associated to the disease, which greatly benefit from early treatment.

2-pentadecyl-2-oxazoline prevents cognitive and social behaviour impairments in the Amyloid ß-induced Alzheimer-like mice model: Bring the α2 adrenergic receptor back into play.

The 2-pentadecyl-2-oxazoline (PEA-OXA) is a natural compound with protective action in neuro-inflammation. We have previously shown that PEA-OXA behaves as an α2 adrenergic receptor (α2AR) antagonist and a putative protean agonist on histamine H3 receptors. Recently, neuroinflammation and monoaminergic neurotransmission dysfunction has drawn particular attention in Alzheimer Disease (AD) pathophysiology. In this context, the objective of this study was to investigate the effects of the dual-acting PEA-OXA in an AD-like model in mice. A combined computational and experimental approach was used to evaluate the ability of PEA-OXA to bind α2A-AR subtype, and to investigate the effects of PEA-OXA treatment on neuropathological (behavioural and functional) effects induced by soluble Amyloid ß 1-42 (sAß1-42) intracerebroventricular injection. Computational analysis revealed the PEA-OXA ability to bind the α2A-AR, a pharmacological target for AD, in two alternative poses, one overlapping the Na+ binding site. In vivo studies indicated that chronic treatment with PEA-OXA (10 mg/kg, os) restored the cognitive (discriminative and spatial memory) deficits and social impairments induced by sAß injection. Consistently, electrophysiological analysis showed a recovery of the long-term potentiation in the hippocampus (Lateral Entorhinal Cortex-Dentate Gyrus pathway), while neuroinflammation, i.e., increased pro-inflammatory cytokines levels and microglia cells density were reduced. These data provide the basis for further investigation of the pro-cognitive aptitude of PEA-OXA by proposing it as an adjuvant in the treatment in AD, for which the available pharmacological approaches remain unsatisfactory. Moreover, this study offers new future direction in research investigating the role of α2AR in neuropsychiatric illness and therapies.

Health-related quality of life (HRQoL) from HIV patients' perspective: comparison of patient-reported outcome (PRO) measures among people living with hiv (PLWH) and other chronic clinical conditions.

BACKGROUND: People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient's reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies. METHODS: A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs. RESULTS: 230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy. CONCLUSIONS: In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice.

A Combined sEMG and Accelerometer System for Monitoring Functional Activity in Stroke.

Remote monitoring of physical activity using bodyworn sensors provides an alternative to assessment of functional independence by subjective, paper-based questionnaires. This study investigated the classification accuracy of a combined surface electromyographic (sEMG) and accelerometer (ACC) sensor system for monitoring activities of daily living in patients with stroke. sEMG and ACC data were recorded from 10 hemi paretic patients while they carried out a sequence of 11 activities of daily living (Identification tasks), and 10 activities used to evaluate misclassification errors (non-Identification tasks). The sEMG and ACC sensor data were analyzed using a multilayered neural network and an adaptive neuro-fuzzy inference system to identify the minimal sensor configuration needed to accurately classify the identification tasks, with a minimal number of misclassifications from the non-Identification tasks. The results demonstrated that the highest sensitivity and specificity for the identification tasks was achieved using a subset of 4 ACC sensors and adjacent sEMG sensors located on both upper arms, one forearm, and one thigh, respectively. This configuration resulted in a mean sensitivity of 95.0 %, and a mean specificity of 99.7 % for the identification tasks, and a mean misclassification error of < 10% for the non-Identification tasks. The findings support the feasibility of a hybrid sEMG and ACC wearable sensor system for automatic recognition of motor tasks used to assess functional independence in patients with stroke.

The fifth cranial nerve in headaches.

The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.

A false positive case of high-sensitivity cardiac troponin in a patient with acute chest pain: Analytical study of the interference.

We report a case of a heterophile antibodies interference in a new high-sensitivity troponin commercial immunoassay (cTNIH Siemens), observed in a patient with possible acute coronary syndrome (ACS). The analytical interference was investigated with standard laboratories procedures. The false positive result was found with different troponin methods and kits. We also investigated the protein sequence of cTnl and no sequence variants were detected. The discordance between clinical pictures and high concentration of cTnl, together with the collaboration between clinicians and laboratory staff avoided possible erroneous diagnosis and further invasive investigations to the patient.

Prenatal diagnosis, natural history, postnatal treatment and outcome of 222 cases of spina bifida: experience of a tertiary center.

OBJECTIVES: To report on the prenatal ultrasonographic diagnosis of spina bifida (SB) and its natural history, treatment and long-term outcome in a large tertiary referral center. METHODS: All cases of SB diagnosed between February 1980 and December 2015 in the Obstetric Prenatal Diagnosis Day Unit of the Obstetrics and Gynecology Department at the Catholic University of the Sacred Heart, Rome, were reviewed. All infants with an open defect were delivered by elective Cesarean section and underwent early repair of the spinal defect. A ventriculoperitoneal (VP) shunt and/or third ventriculostomy was performed when needed. Complete postnatal follow-up was carried out by our multidisciplinary team in the majority of cases. The cohort was analyzed in two groups: Group 1 included patients referred between February 1980 and December 1999; Group 2 included patients referred between January 2000 and December 2015. RESULTS: There was a total of 222 cases of SB with a prenatal diagnosis rate of 94.6% (n = 210), with the majority of defects being meningomyeloceles (n = 142 (64.0%)), affecting the lumbosacral level (n = 110 (49.5%)) and being ≥ 2 cm in size (n = 163/195 (83.6%)). There were 174 (78.4%) live births, with more terminations in Group 2 (26.1%) than in Group 1 (10.8%; P = 0.003). Postnatal surgical repair was conducted in 157 cases (99.4% of eligible cases), with death of an infant who was operated on occurring more often in Group 1 (14.1%) than in Group 2 (4.2%; P = 0.03). VP shunt placement was required in 60.3% of infants operated on after January 2000. Long-term follow-up was available for 136 children (111 with open defects and 25 with closed defects). Infants born since 2000 with an open defect had normal ambulation or a mild defect in 50% of cases and normal or mild deficit of sphincter function in 37.8% of cases. An intelligence quotient of ≥ 70 was observed in the majority of children (81.4%; 35/43 cases). Worse motor function was associated with progressive prenatal ventriculomegaly, level of lesion and VP shunt placement. CONCLUSIONS: We describe the prenatal diagnosis, natural history and long-term outcome of a large contemporary cohort of SB fetuses and infants. In an era of pioneering fetal surgical techniques for in-utero SB repair, it is important to acknowledge that advances in conventional neonatology and pediatric neurosurgery have allowed increased life expectancy and improved quality of life in patients with SB. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Reducing rates of Clostridium difficile infection by switching to a stand-alone NAAT with clear sampling criteria.

Background: Clostridium difficile infection is an important cause of morbidity and mortality but the optimal method of diagnosis for both patient management and infection prevention remains controversial. Methods: Our hospital made a decision to switch from the use of toxin immunoassay to a stand-alone nucleic acid test. This change was accompanied by the provision of clear sampling guidance and rejection criteria and this study aimed to assess the impact of that change. We analysed sample numbers, numbers of positive results, and the proportion of cases assessed as healthcare acquired over a 6-year period during which the testing method was changed from a toxin A/B immunoassay to a stand-alone commercial nucleic acid test after the first two years. Results: Sample numbers and numbers of cases assessed as healthcare acquired fell following the introduction of the nucleic acid test and sampling guidance, while infection rates in other hospitals in the same region remained relatively stable. Conclusions: It is our opinion that the use of a highly sensitive assay together with clear sampling guidance offers the optimal approach to patient management and best use of isolation facilities.

Epidemiology and clinics of mushroom poisoning in Northern Italy: A 21-year retrospective analysis.

BACKGROUND: Limited information exists about epidemiology and management of mushroom poisoning. We analyzed and described epidemiology, clinical presentation, and clinical course of mushroom-poisoned patients admitted to emergency departments (EDs) of the Province of Parma, Italy. METHODS: Data from the database of mycological service were matched with clinical information retrieved from hospitals' database, from January 1, 1996 to December 31, 2016. RESULTS: Mycologist consultation was obtained in 379/443 identified mushroom poisonings. A remarkable seasonality was found, with significant peak in autumn. Thanks to the collaboration, the implicated species could be identified in 397 cases (89.6%); 108 cases (24.4%) were due to edible mushrooms, Boletus edulis being the most represented (63 cases). Overall, 408 (92%) cases presented with gastrointestinal toxicity. Twenty cases of amatoxin poisoning were recorded (11 Amanita phalloides and 9 Lepiota brunneoincarnata). One liver transplantation was needed. We observed 13 cases of cholinergic toxicity and 2 cases of hallucinogenic toxicity. Finally, 46 cases were due to "mixed" toxicities, and a total of 69 needed hospitalization. CONCLUSIONS: Early identification and management of potentially life-threatening cases is challenging in the ED, so that a mycologist service on call is highly advisable, especially during periods characterized by the highest incidence of poisoning.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone.

Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans.

Challenges and opportunities of next-generation sequencing: a cytopathologist's perspective.

Molecular cytopathology has gene sequencing as its core technology. Until recently, cytological samples were only tested by sequential single-gene mutational tests. Today, with the better understanding of the molecular events involved in malignancy and the mechanisms of pharmacotherapy, larger gene panels are more informative than a single biomarker. Next-generation sequencing (NGS), matched with the multiplex capture of targeted gene regions and analysed by sophisticated bioinformatics tools, enables the simultaneous detection of multiple mutations in multiple genes. With the development of miniaturised technology and benchtop sequencers, it is not unlikely that NGS will soon be adopted for routine molecular diagnostics, including cytological samples. This review addresses (1) the most relevant methodological and technical aspects of the NGS analysis workflow and the diverse platforms available; (2) the issues related to daily practice implementation, namely, the cytological sample requirement and the validation procedures; and (3) the opportunities that NGS offers in different fields of cytopathology, to increase mutation detection sensitivity in paucicellular smears and to extend the analysis to a larger number of gene regions. Cytopathologists involvement and coordination in this rapidly evolving field is crucial for the effective implementation of NGS in the present and future cytological practice.

Performance of EGFR mutant-specific antibodies in different cytological preparations: a validation study.

OBJECTIVES: Molecular testing for epidermal growth factor receptor (EGFR) mutations is required to select the most appropriate treatment for advanced-stage non-small cell lung cancer (NSCLC). In routine practice, cytological samples are often the only specimens available for testing. When the number of neoplastic cells is large, DNA-based assays are the gold standard. When cytological samples contain only a few neoplastic cells, immunocytochemistry (ICC) using anti-EGFR mutant-specific antibodies may be more effective. We aim to assess the specificity and sensitivity of IHC staining in cytological specimens using mutated cell lines subjected to different cytopreparations and staining methods. METHODS: HCC827 (exon 19 p.E746-A750 del) and H3255 (exon 21 p.L858R) cell lines were subjected to different fixation (air dried, alcohol or CytoLyt(®)), staining (Diff-Quik(®) or Papanicolaou) and preparation (smears or cell blocks) methods before ICC. In a second set of experiments, mutated cells were mixed with EGFR wild-type cells to obtain low-level (10%) mutated cytological samples. The intensity and percentage of cells stained were evaluated against validated molecular techniques. Moreover, the cell lines were subjected to poor growing conditions to simulate routine specimens that are less optimal than in vitro samples. RESULTS: The cytological preparations showing the most intense staining were formalin-fixed cell blocks and samples fixed with CytoLyt or alcohol, including Papanicolaou-destained samples. Conversely, air-dried slides showed the least intense staining. Mutant antibodies allowed the detection of mutated cells, even when representing only 10% of the total population. Although, in necrotic specimens, an aspecific background signal appeared, the viable cells still retained anti-mutant EGFR positivity. CONCLUSIONS: All cytological preparations are suitable for ICC using anti-EGFR mutant-specific antibodies, in particular formalin-fixed cell blocks and alcohol- or CitoLyt-fixed samples. the method is also validated to detect even a few mutant cells in less than optimal samples.

Outsourcing cytological samples to a referral laboratory for EGFR testing in non-small cell lung cancer: does theory meet practice?

OBJECTIVE: Guidelines from the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC) and the Association for Molecular Pathology (AMP) consider cytology suitable for testing epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. The guidelines recommend that cytopathologists first discuss the possibility of testing squamous cell carcinomas (SqCC) in multidisciplinary meetings. Second, cell blocks should be analysed rather than smear preparations and, third, specimens should be sent to external molecular laboratories within three working days of receiving requests. This study monitored how these recommendations are met in practice. METHODS: Our laboratory received 596 requests from cytologists from 13 different institutions. For each case, the cytological diagnosis, cytopreparation type, and time between the request and sample mailing were compared with the recommendations. RESULTS: Of the 596 samples, 32 (5.4%) had been reported as SqCC. Three of these (9.4%) showed EGFR mutation. Cytological slides, either ThinPrep(™) (51.2%) or direct smears (43.2%), were more frequently received than cell blocks (5.7%). The mean time between the oncologist's request and specimen dispatching was 5.8 working days. CONCLUSIONS: The occurrence of mutations in samples reported as SqCC was higher than expected. This questions the reliability of the original diagnosis, which reinforced the recommendation to evaluate the opportunity for testing non-adenocarcinoma cytology on a case-by-case basis. In spite of CAP/IASLC/AMP recommendations, cell blocks were underutilized for EGFR testing, but cytological slides were suitable for DNA analyses. Significant efforts are needed to avoid delays in outsourcing cytological samples for EGFR testing.

OPSI threat in hematological patients.

Overwhelming post-splenectomy infection (OPSI) is a rare medical emergency, mainly caused by encapsulated bacteria, shortly progressing from a mild flu-like syndrome to a fulminant, potentially fatal, sepsis. The risk of OPSI is higher in children and in patients with underlying benign or malignant hematological disorders. We retrospectively assessed OPSI magnitude in a high risk cohort of 162 adult splenectomized patients with malignant (19%) and non malignant (81%) hematological diseases, over a 25-year period: 59 of them splenectomized after immunization against encapsulated bacteria, and 103, splenectomized in the previous 12-year study, receiving only life-long oral penicillin prophylaxis. The influence of splenectomy on the immune system, as well as the incidence, diagnosis, risk factors, preventive measures and management of OPSI are also outlined. OPSI occurred in 7 patients (4%) with a median age of 37 years at time interval from splenectomy ranging from 10 days to 12 years. All OPSIs occurred in non immunized patients, except one fatal Staphylococcus aureus -mediated OPSI in a patient adequately immunized before splenectomy. Our analysis further provides evidence that OPSI is a lifelong risk and that current immune prophylaxis significantly decreases OPSI development. Improvement in patients' education about long-term risk of OPSI and increased physician awareness to face a potentially lethal medical emergency, according to the current surviving sepsis guidelines, represent mandatory strategies for preventing and managing OPSI appropriately.

A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade.

PURPOSE: The aim of this study was to assess the epidemiology of candidemia and antifungal susceptibility profiles of Candida isolates in Italy through a prospective surveillance study and to evaluate changes compared to a previous survey performed in one Italian region (Lombardy) in 1997-1999. METHODS: A prospective laboratory-based surveillance of candidemia was performed in Italy from January to December 2009. For each case a questionnaire was filled in, and the first isolate was collected and tested for in vitro antifungal susceptibility. RESULTS: During our 12-month survey, 467 episodes of candidemia were reported from 34 centres (30 located in Lombardy) and 464 isolates collected. Candida albicans was the predominant species (overall incidence 50.4 %), but the proportion varied considerably from 52.1 % in Lombardy hospitals to 45.2 % hospitals located outside this region. The second most frequent species was C. glabrata in Lombardy and C. parapsilosis in other regions. Comparison of the 1997-1999 and 2009 data on episodes of candidemia in Lombardy revealed a threefold increase in incidence (from 0.38 to 1.19 per 1,000 admissions), aging of infected patients, decline in crude mortality (from 35 to 27.1 %) and an increased proportion of C. glabrata etiology (from 12.8 to 20.3 %). Susceptibility testing confirmed the broad activity of amphotericin B and echinocandins. Decreased susceptibility to fluconazole was found in 24.9 % of the tested isolates. CONCLUSIONS: The results of this latest survey confirm the high rate of candidemia in Italy and show changes in some of the epidemiological tracts, such as aging of infected patients, increased proportion of C. glabrata infections, increased diagnosis in medical wards, and improvement in patients' survival.

A novel vibratory stimulation-based occlusal splint for alleviation of TMD painful symptoms: a pilot study.

This pilot study introduces a novel vibratory stimulation-based occlusal splint (VibOS) for management of pain related to temporomandibular disorders (TMD). The study sample consisted of 10 patients (mean age: 40·5 ± 13·7 years, male/female: 3/7) who were using stabilisation splints for more than 2 months prior to the study onset and still complained of pain. Patients utilised the active and inactive VibOS during 15 days in a crossover designed clinical trial. The analysed variables were self-reported VAS pain levels and number of painful sites to palpation (PSP). Statistical analysis was performed with repeated measures anova. At baseline, mean VAS pain levels for group I and II were 45·6 ± 21·0 mm and 37·4 ± 16·3 mm, respectively. Comparison between these baseline values showed no statistical difference (P > 0·05, unpaired t-test). In group I, the inactive VibOS caused a slight increase in VAS pain levels, whereas the active VibOS promoted a significant decrease in VAS pain levels and PSP (P < 0·01). In group II, which received the active VibOS first, a significant decrease in VAS levels (P < 0·05) and in PSP (P < 0·01) was observed. No significant decrease in VAS pain levels or PSP (P > 0·05) was observed with the use of the inactive VibOS. In conclusion, this study demonstrated a good tendency of this novel VibOS in the alleviation of painful symptoms related to TMD after a 15-day management period compared to control VibOS.

Piroxicam and laser phototherapy in the treatment of TMJ arthralgia: a double-blind randomised controlled trial.

This study aimed to evaluate the efficacy of piroxicam associated with low-level laser therapy compared with single therapies in 32 patients presenting temporomandibular joint arthralgia in a random and double-blind research design. The sample, divided into laser + piroxicam, laser + placebo piroxicam and placebo laser + piroxicam groups, was submitted to the treatment with infrared laser (830 nm, 100 mW, 28 s, 100 J cm(-2) ) at 10 temporomandibular joint and muscle points on each side during four sessions concomitant to take one capsule a day of piroxicam 20 mg during 10 days. The treatment was evaluated throughout four sessions and 30 days follow-up through visual analogue scale (VAS), maximum mouth opening and joint and muscle (temporal and masseter) pain on palpation. The results showed that all the study groups had a significant improvement in the VAS scores (P < 0·05), and there were no significant group differences. Piroxicam was effective in the reduction of joint and muscle pain on palpation (P < 0·05) and showed the lowest temporal pain (P = 0·02) at the 30-day follow-up. The combination of low-level laser therapy and piroxicam was not more effective than single therapies in the treatment of temporomandibular joint arthralgia. The use of piroxicam was more effective in the following 30 days.

New molecular and cellular targets for chemoprevention and treatment of skin tumors by plant polyphenols: a critical review.

As the incidence of skin tumors has been steadily growing, there is an urgent need for the preventive measures as well as the improved therapeutic approaches. In the last two decades, natural plant derived polyphenols (PPs, resveratrol, silibinin, green tea polyphenols, flavonoids, anthocyanins, etc.) have been drawing particular interest as emerging active substances in dermatological/cosmeceutical compositions for the prevention, slowing, or reversion of skin tumorigenesis (chemoprevention). When chronically applied to the skin, they supposedly would not damage normal skin cells or negatively affect their functions while they would suppress tumorigenic cell transformation, inhibit tumor cell proliferation, and activate tumor cell apoptosis. PPs are also reported to synergize with conventional anti-cancer therapies. The major aim of this critical review is to provide recent updates on the molecular and cellular targets for the prevention and therapy of skin tumors with a special focus on the crossroad between inflammation and carcinogenesis as the most promising approach to chemoprevention. Novel therapeutic targets as different as epidermal stem cells, cellular senescence, epigenetic enzymes involved in carcinogenesis, epidermal growth factor and aryl hydrocarbon receptors, and metabolic CYP1 subfamily enzymes are highlighted. The mechanisms of PPs interaction with these molecular and cellular targets are reviewed. The feasibility of PPs to prevent/ cure specific cutaneous toxicity connected to anti-EGFR therapy and to reduce multidrug resistance of skin tumors is also discussed.