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Purpose: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. Methods: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. Results: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. Conclusions: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3. [ABSTRACT FROM AUTHOR]

We introduce supergroup analogs of 3-manifold invariants Z ^ , also known as homological blocks, which were previously considered for ordinary compact semisimple Lie groups. We focus on superunitary groups and work out the case of SU(2|1) in details. Physically these invariants are realized as the index of BPS states of a system of intersecting fivebranes wrapping a 3-manifold in M-theory. As in the original case, the homological blocks are q-series with integer coefficients. We provide an explicit algorithm to calculate these q-series for a class of plumbed 3-manifolds and study quantum modularity and resurgence properties for some particular 3-manifolds. Finally, we conjecture a formula relating the Z ^ invariants and the quantum invariants constructed from a non-semisimple category of representation of the unrolled version of a quantum supergroup. [ABSTRACT FROM AUTHOR]

Purpose: Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. Methods: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. Results: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. Conclusions: Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients. [ABSTRACT FROM AUTHOR]

By studying the properties of q-series Z ^ -invariants, we develop a dictionary between 3-manifolds and vertex algebras. In particular, we generalize previously known entries in this dictionary to Lie groups of higher rank, to 3-manifolds with toral boundaries, and to BPS partition functions with line operators. This provides a new physical realization of logarithmic vertex algebras in the framework of the 3d-3d correspondence and opens new avenues for their future study. For example, we illustrate how invoking a knot-quiver correspondence for Z ^ -invariants leads to many infinite families of new fermionic formulae for VOA characters. [ABSTRACT FROM AUTHOR]

Due to the importance of joint disease and ostearthritis (OA) in equine athletes, new regenerative treatments to improve articular cartilage repair after damage are gaining relevance. Chondrocyte de-differentiation, an important pathogenetic mechanism in OA, is a limiting factor when differentiated articular chondrocytes are used for cell-based therapies. Current research focuses on the prevention of this de-differentiation and/or on the re-differentiation of chondrocytes by employing different strategies in vitro and in vivo. Articular chondrocytes normally live in a condition of higher osmolarity (350–450 mOsm/L) compared to normal physiological fluids (~ 300 mOsm/L) and some studies have demonstrated that osmolarity has a chondroprotective effect in vitro and in vivo. Therefore, the response of horse articular chondrocytes to osmolarity changes (280, 380, and 480 mOsm/L) was studied both in proliferating, de-differentiated chondrocytes grown in adhesion, and in differentiated chondrocytes grown in a 3D culture system. To this aim, cell proliferation (cell counting), morphology (optical microscopy), and differentiation (gene expression of specific markers) were monitored along with the expression of osmolyte transporters involved in volume regulation [betaine-GABA transporter (BGT-1), taurine transporter (SLC6A6), and neutral amino acid transporter (SNAT)] real-time qPCR. Proliferating chondrocytes cultured under hyperosmolar conditions showed low proliferation, spheroidal morphology, a significant reduction of de-differentiation markers [collagen type I (Col1) and RUNX2] and an increase of differentiation markers [collagen type II (Col2) and aggrecan]. Notably, a persistently high level of BGT-1 gene expression was maintained in chondrocyte cultures at 380 mOsm/L, and particularly at 480 mOsm/L both in proliferating and differentiated chondrocytes. These preliminary data encourage the study of osmolarity as a microenvironmental co-factor to promote/maintain chondrocyte differentiation in both 2D and 3D in vitro culture systems. [ABSTRACT FROM AUTHOR]

Background: During the Sars-CoV-2 virus pandemic, Italy faced an unrivaled health emergency. Its impact has been significant on the hospital system and personnel. Clinical neurophysiology technicians played a central role (but less visibly so compared to other healthcare workers) in managing the COVID-19 pandemic. This research aims to explore the experiences of clinical neurophysiology technicians during the pandemic and contribute to the debate on the well-being of healthcare workers on the front line. Methods: We implemented a cross-sectional survey across Italy. It contained questions that were open-ended for participants to develop their answers and acquire a fuller perspective. The responses were analyzed according to the framework method. Results: One hundred and thirty-one responses were valid, and the following themes were generated: technicians' experiences in their relationship with patients, technicians' relationship with their workgroup and directors, and technicians' relationship with the context outside of their work. The first theme included sub-themes: fear of infection, empathy, difficulty, a sense of obligation and responsibility, anger, and sadness. The second theme contained selfishness/solidarity in the workgroup, lack of protection/collaboration from superiors, stress, and distrust. The last theme included fear, stress/tiredness, serenity, sadness, and anger. Conclusion: This study contributes to building a humanized perspective for personnel management, bringing attention to the technical work of healthcare professionals in an emergency and the emotional and relational dimensions. These are the starting points to define proper, contextually adequate support. [ABSTRACT FROM AUTHOR]

The availability of a reliable molecular assay in species recognition in forensic cases is of paramount importance when visual inspection or morphological methods are not exhaustive, especially from challenging samples. Here, two different caseworks involving bone samples founded during medico-legal outdoor investigations are presented. In order to exclude the human nature of the specimens and to determine the exact species they belong to, we proceeded with the molecular approach trying to generate sequences from the classical mtDNA markers cyt b and COI. However, they both gave critical results. For this reason, a short amplicon of ~ 150 bp of the 12S rRNA gene was used as an alternative.This short fragment was sufficient to identify the biological origin of the bone specimens with a high degree of certainty leading to the exclusion of their human nature. This work highlights the utility of the 12S rRNA and underlines the importance of deepen the choice of alternative shorter markers with respect to the classical ones, in order to achieve species identification even from challenging and degraded material in forensic criminal and wildlife caseworks. [ABSTRACT FROM AUTHOR]

This paper is aimed at studying the thermal properties of poly(lactic acid), PLA with different plasticizers. Plasticized PLA was obtained by mixing and extruding PLA with 20 mass% of neat cardanol, epoxidized cardanol acetate (ECA) and poly(ethylene glycol) (PEG) 400. The glass transition of completely amorphous samples, melting and crystallization behavior of plasticized PLA were analyzed by differential scanning calorimetry. Results obtained show that, below Tg, a higher enthalpy relaxation occurs for PLA plasticized by cardanol derivatives. This is indicative of a faster mobility of PLA chains below Tg, when cardanol derivatives are used as plasticizers. On the other hand, an opposite behavior was observed for the crystallization studies. In facts, a much faster crystallization was found for PLA plasticized by PEG, which in turn indicates a much higher mobility of PLA chains above Tg compared to PLA plasticized by cardanol derivatives. Mechanical properties obtained on completely amorphous samples show that PLA plasticized by ECA is characterized by lower modulus, which is indicative of a more efficient plasticization. On the other hand, the thicker crystals formed during crystallization of PLA plasticized by ECA involve a more relevant increase in the modulus in semicrystalline samples. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 virus infection is responsible for coronavirus disease (COVID-19), which is characterised by a hyperinflammatory response that plays a major role in determining the respiratory and immune-mediated complications of this condition. While isolating peripheral blood mononuclear cells (PBMCs) from whole blood of COVID-19 patients by density gradient centrifugation, we noticed some changes in the floating properties and in the sedimentation of the cells on density medium. Investigating this further, we found that in early phase COVID-19 patients, characterised by reduced circulating lymphocytes and monocytes, the PBMC fraction contained surprisingly high levels of neutrophils. Furthermore, the neutrophil population exhibited alterations in the cell size and in the internal complexity, consistent with the presence of low density neutrophils (LDNs) and immature forms, which may explain the shift seen in the floating abilities and that may be predictive of the severity of the disease. The percentage of this subset of neutrophils found in the PBMC band was rather spread (35.4 ± 27.2%, with a median 28.8% and IQR 11.6–56.1, Welch's t-test early phase COVID-19 versus blood donor healthy controls P < 0.0001). Results confirm the presence of an increased number of LDNs in patients with early stage COVID-19, which correlates with disease severity and may be recovered by centrifugation on a density gradient together with PBMCs. [ABSTRACT FROM AUTHOR]

In recent years, the exploitation of natural resources and industrial development have led to the production of harmful pollutants. Much of these contaminants end up in water resources, reducing the availability of drinking water. Therefore, it is necessary to find remedies to this situation. Solutions could be the adsorption or the degradation through photocatalysis of these compounds. A good candidate for this task is titanium dioxide (TiO2), due to its non-toxicity, stability and low cost. In this work, we propose a novel synthesis of TiO2 nanoparticles (NPs), with high adsorption capacity, produced at low temperature in alkaline environment. Adsorption tests were conducted using methylene blue and diclofenac as model pollutants. Moreover, the obtained NPs have been characterized through Raman spectroscopy, Scanning and Transmission electron microscopies and with thermogravimetric analysis. The results showed a porous structure with a high surface area, able to efficiently adsorb large amounts of dye from the aqueous solution. These properties make the obtained TiO2 powders suitable for applications devoted to the adsorption and recovery of harmful compounds. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30–40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes' cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the epidemiology of male breast cancer (MBC) in Italy and to describe incidence and survival data in relation to age, morphology, year of incidence, geographic area, and possible association with other cancers compared with female BC. Methods: Cases were extracted from 40 Italian Cancer Registries. Standardized incidence rates (SIR), age-specific rates, and 5-year survival were calculated. The association with second tumors was also evaluated. All data were compared with data from female BCs. Results: In the 2000–2014 period, 2175 new cases of MBC were registered, with an SIR of 1.7 × 100,000. The incidence showed a slight upward trend and increased with increasing age. The 5-year survival was 82% in the first two periods (2000–2004, 2005–2009), lower than in females (87%). The most frequent morphology was the ductal carcinoma (84%). Stage at diagnosis was 39.5% stage I, 33.1% stage II, 20.9% in stage III, and 6.4% in stage IV. Concerning receptor status, 96.4% had ER+ and 82.5% PR+; 46.5% had high Ki67 and 14.7% HER2 amplified. The risk of BC increased if the man had already had a previous tumor in any site (excess absolute risk, EAR = 2.7) and especially if he had had prostate cancer (EAR = 5.1). Instead, males with a previous diagnosis of BC had an increased risk of testicular, kidney and lung cancer. Conclusions: MBC requires more attention in terms of diagnosis and treatment as clinicians tend to follow the guidelines that have been developed for female BC management. [ABSTRACT FROM AUTHOR]

The control and the execution of motor tasks are largely influenced by proprioceptive feedback, i.e. the information about the position and movement of the body. In 1972, it was discovered that a vibratory stimulation applied non-invasively to a muscle or a tendon induces a movement illusion consistent with the elongation of the vibrated muscle/tendon. Although this phenomenon was reported by several studies, it is still unclear how to reliably reproduce it because of the many different features of the stimulation altering the sensation (e.g. frequency, duration, location). By performing a psychophysical test, we analysed the effects of the stimulation point and the preload force on the minimum stimulation amplitude needed to elicit an illusion of movement. In particular, we stimulated two groups of healthy subjects on three target regions of the biceps brachii muscle (the distal tendon, the muscle belly and one of the proximal tendons) applying three preload force ranges (0.5-0.75N, 1-2N and 3-4N). Our results showed that the minimum stimulation amplitude eliciting a sensation is affected by the preload force. On the contrary, it did not change significantly among the three stimulated regions. Nevertheless, the reported vividness of the illusion of movement changed across the stimulated points decreasing while moving from the distal to the proximal tendons. Overall, these outcomes contribute to the scientific debate on the features that modulate the vibration-induced movement illusion proposing ways to increase the reliability of the procedure in basic and applied research studies. [ABSTRACT FROM AUTHOR]

This work is aimed to the development of a self-healing thermoplastic matrix nanocomposite, obtained through the ring-opening polymerization of cyclic butylene terephthalate (CBT) to polybutylene terephthalate (pCBT); a partial polymerization allows obtaining a mixture of CBT and pCBT, being the two materials characterized by a difference in the melting temperature of about 80 °C. Healing of the material requires heating to a temperature higher than melting of CBT, but lower than melting of pCBT; therefore, the molten CBT is able to weld the surfaces of the growing crack, thus restoring mechanical properties. The presence of solid pCBT allows retaining the geometry of the material. In order to produce a partially polymerized material, two different systems were studied: a first one with two catalysts, with different activation temperatures, and a second one with one single catalyst partially intercalated in nanoclay layers. Rheological analysis was used in order to study the viscosity evolution associated with the conversion of CBT to pCBT during thermal treatment. Differential scanning calorimetry (DSC) was used in order to measure the amount of unreacted CBT after processing, and to verify the further conversion of CBT to pCBT during healing. Also, DSC analysis highlighted the structural changes of pCBT crystallinity during healing. Flexural tests were performed on partially reacted pCBT samples, highlighting the relevant effect of the addition of nanoclay on the mechanical properties of the material. Adhesion tests performed after healing evidenced the efficacy of the proposed approach for development of self-healing thermoplastic polymers. [ABSTRACT FROM AUTHOR]

This work is aimed to study the suitability of cardanol and its derivatives as plasticizers for poly(lactic acid), PLA. Differential scanning calorimetry (DSC) was used to assess the plasticizing effectiveness of cardanol (CARD) and its derivatives, cardanol acetate and epoxidated cardanol acetate, comparing the results with those obtained with a commercially available plasticizer, poly (ethylene glycol), PEG, with an average molecular weight of 400 g mol−1. Measurement of the glass transition temperature highlighted that, among the tested cardanol derivatives, neat cardanol is the most effective plasticizer for PLA. In fact, the glass transition temperature of PLA plasticized by CARD is only slightly higher than that of PLA plasticized by PEG. This is attributed to the lower compatibility between PLA and CARD compared to PLA and PEG, as estimated by the interaction radius. Therefore, cardanol could represent a technically valid, economic, and largely available plasticizer for PLA. Moreover, DSC, an X-ray diffraction analysis, showed that, compared to PEG, the addition of CARD involves a limited increase of the rate of crystallization, even in this case, due to its lower compatibility with PLA. Dynamic mechanical analysis showed that, below glass transition, PEG is able to reduce the stiffness of PLA by a higher extent. However, as the temperature increases, retention of the shear modulus of PEG-plasticized PLA is much higher than that of CARD-plasticized PLA. As a consequence, above glass transition, the stiffness of CARD-plasticized PLA becomes lower than that of PEG-plasticized PLA. Therefore, despite its lower compatibility with PLA, CARD can impart to plasticized PLA lower modulus compared to PEG, when the plasticizer content is high enough to reduce the glass transition below room temperature. [ABSTRACT FROM AUTHOR]

Aim: To summarize evidence on the effectiveness of educational interventions for type 2 diabetes control in South Asians living in high-income countries. Methods: We systematically searched PubMed, EMBASE, Cinahl and the Cochrane Library, using Medical Subject Heading and free-text terms. The considered outcomes were: mortality, morbidity, glycaemic control, blood pressure, practice (diet, physical activity and self-care), attitudes/awareness and knowledge. Papers published up to July 2015 were considered. Two reviewers independently screened the title and abstract and then read the full text of selected papers. Results: Nine studies were included, four non-randomized studies of interventions and five randomized controlled trials. All studies except one were conducted in the UK. Target population ranged from 39 to 1486 individuals; the follow-up ranged from 1 to 24 months. The interventions were mostly based on a tailored educational package, individually or group administered, conducted by lay link workers, health professionals or both. No study measured mortality or morbidity. An effect on glycaemic control was observed only in before/after studies, while a randomized study showed a non-significant improvement (percentage of glycated haemoglobin −0.15, P = 0.11). Two randomized studies found a reduction in blood pressure. Changes in practice and attitudes showed heterogeneous results, mostly favouring intervention. Conclusions: There was weak evidence that interventions using link workers and tailored education can modify attitudes, self-care skills and blood pressure in South Asian migrants to industrialized countries. Only one larger trial, with adequate follow-up, showed a small non-significant improvement of glycaemic control. [ABSTRACT FROM AUTHOR]

Background: Clinical options for patients harbouring advanced/recurrent uterine serous carcinoma (USC), an aggressive variant of endometrial tumour, are very limited. Next-generation sequencing (NGS) data recently demonstrated that cyclin E1 (CCNE1) gene amplification and pik3ca driver mutations are common in USC and may therefore represent ideal therapeutic targets.Methods: Cyclin E1 expression was evaluated by immunohistochemistry (IHC) on 95 USCs. The efficacy of the cyclin-dependent kinase 2/9 inhibitor CYC065 was assessed on multiple primary USC cell lines with or without CCNE1 amplification. Cell-cycle analyses and knockdown experiments were performed to assess CYC065 targeting specificity. Finally, the in vitro and in vivo activity of CYC065, Taselisib (a PIK3CA inhibitor) and their combinations was tested on USC xenografts derived from CCNE1-amplified/pik3ca-mutated USCs.Results: We found that 89.5% of the USCs expressed CCNE1. CYC065 blocked cells in the G1 phase of the cell cycle and inhibited cell growth specifically in CCNE1-overexpressing USCs. Cyclin E1 knockdown conferred increased resistance to CYC065, whereas CYC065 treatment of xenografts derived from CCNE1-amplified USCs significantly reduced tumour growth. The combination of CYC065 and Taselisib demonstrated synergistic effect in vitro and was significantly more effective than single-agent treatment in decreasing tumour growth in xenografts of CCNE1-amplified/pik3ca-mutated USCs.Conclusions: Dual CCNE1/PIK3CA blockade may represent a novel therapeutic option for USC patients harbouring recurrent CCNE1-amplified/pi3kca-mutated tumours. [ABSTRACT FROM AUTHOR]

Purpose: Several authors have described zygoma implants as a reliable surgical option to rehabilitate severe maxillary defects in case of extreme atrophy or oncological resections. The aim of this study is to report a new technical approach to the rehabilitation of a complex oronasal defect by means of a zygoma-implant-supported full-arch dental prosthesis combined with a nasal epithesis. Patients and methods: The patient presented with a subtotal bilateral maxillectomy and total rhinectomy defect because of a squamous cell carcinoma of the nose. No reconstructive surgery was performed because of the high risk of recurrence; moreover, the patient refused any secondary procedure. After surgery, the patient presented a wide palatal defect associated to the absence of the nasal pyramid. Zygoma-retained prostheses are well documented, and they offer good anchorage in rehabilitating wide defects after oncological surgery and a good chance for patients to improve their quality of life. We hereby describe two prosthetic devices rehabilitating two iatrogenic defects by means of a single intraoral implant-supported bar extending throughout the oronasal communication, thus offering nasal epithesis anchorage. Results: At 1-year follow-up after functional prosthetic loading, no implant failure has been reported. Clinical and radiological follow-up showed no sign of nasal infection or peri-implantitis. The patient reported a sensitive improvement of his quality of life. Conclusions: Simultaneous oral and nasal rehabilitation of complex oronasal defects with zygoma-implant-supported dental prosthesis and nasal epithesis represents a reliable surgical technique. According to this clinical report, the above-mentioned technique seems to be a valuable treatment option as it is safe, reliable and easy to handle for both surgeon and patient. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the role of PIK3CA-mutations as mechanism of resistance to trastuzumab in primary HER2/neu-amplified uterine-serous-carcinoma (USC) cell lines.Methods: Fifteen whole-exome-sequenced USC cell lines were tested for HER2/neu-amplification and PIK3CA-mutations. Four HER2/neu-amplified USC (2-harbouring wild-type-PIK3CA-genes and 2-harbouring oncogenic-PIK3CA-mutations) were evaluated in in vitro dose-titration-proliferation-assays, cell-viability and HER2 and S6-protein-phosphorylation after exposure to trastuzumab. USC harbouring wild-type-PIK3CA were transfected with plasmids encoding oncogenic PIK3CA-mutations (i.e., H1047R/R93Q) and exposed to trastuzumab. Finally, trastuzumab efficacy was tested by using two USC xenograft mouse models.Results: Seven out of fifteen (46%) of the USC cell lines were HER2/neu-amplified by fluorescence in situ hybridisation. Within these tumours four out of seven (57%) were found to harbour oncogenic PIK3CA-mutations vs two out of eight (25%) of the HER2/neu not amplified cell lines (P=0.01). HER2/neu-amplified/PIK3CA-mutated USC were highly resistant to trastuzumab when compared with HER2/neu-amplified/wild-type-PIK3CA cell lines (P=0.02). HER2/neu-amplified/PIK3CA wild-type cell lines transfected with oncogenic PIK3CA-mutations increased their resistance to trastuzumab (P<0.0001). Trastuzumab was effective in reducing tumour growth (P=0.001) and improved survival (P=0.0001) in mouse xenografts harbouring HER2-amplified/PIK3CA wild-type USC but not in HER2-amplified/PIK3CA-mutated tumours.Conclusions: Oncogenic PIK3CA mutations are common in HER2/neu-amplified USC and may constitute a major mechanism of resistance to trastuzumab treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Colorectal cancer (CRC) screening using the fecal occult blood test (FOBT) has been shown to be effective in reducing cause-specific mortality. However, although it detects pre-cancerous adenomas, it is uncertain whether FOBT reduces the incidence of invasive cancer. The objective is to evaluate the impact of screening with immunochemical FOBT (FIT) on CRC incidence and mortality.METHODS:An organized screening program was implemented in 2005 in the province of Reggio Emilia (Northern Italy). The program invites the resident population aged 50-69 for FIT every 2 years. Subjects who test positive are referred for colonoscopy. Incidence was studied through cancer registry. Person-times of people aged 50-74 from 1997 to 2012 were classified for exposure to screening according to age and period. Furthermore, two open cohorts-one never screened (aged 50-69 in 1997) and one invited for screening (aged 50-69 in 2005)-were followed up for 8 years.RESULTS:A total of 171,785 people have been invited, and approximately 70% have undergone FIT at least once (272,197 tests). The rate of colonoscopy participation has been about 90%, and 2896 cancers have been recorded (1237 in the screening period). The age-adjusted and sex-adjusted incidence rate ratios as compared with pre-screening were 1.60 (95% confidence interval (CI), 1.43-1.79), 0.86 (95% CI, 0.78-0.94), and 0.59 (95% CI, 0.50-0.69) for the first round, subsequent rounds, and post screening, respectively. Cumulative incidence and incidence-based mortality decreased by 10% (95% CI, 3-17%) and 27% (95% CI, 15-37%), respectively.CONCLUSIONS:FIT screening leads to a decrease in the incidence of CRC and in its mortality. [ABSTRACT FROM AUTHOR]

A number of animal behavioural models were used to study the activity of imidazole (IMID) on the central nervous system. IMID antagonized in a dose-related fashion penile erections (PE) as well as stretching and yawning (SY) elicited in male rats by B-HT 920, an α and dopamine (DA) autoreceptor agonist. Inhibition of B-HT 920-induced PE and SY was also exhibited by haloperidol, a DA receptor blocker, and yohimbine, but not by prazosin, α and α receptor antagonists respectively. Moreover IMID behaved similarly to yohimbine in: 1) counteracting clonidine-induced hypothermia in mice; 2) antagonizing sedation and sleep induced by clonidine and B-HT 920 in chicks, while haloperidol was ineffective. When administered to sexually active rats before the copulatory test, IMID at low doses, significantly altered some aspects of mating, a result which is interpretable in terms of enhanced sexual arousal and resembling the aphrodisiac effect reported for yohimbine. The neurochemical mechanisms involved in these effects are discussed. [ABSTRACT FROM AUTHOR]

Cimetidine injected IP 15 min before (±) N- n-propylnorapomorphine (NPA) antagonized in dose-dependent fashion the penile erections (PE) and stretching and yawning (SY) induced by this typical dopaminergic agonist in male rats. Ranitidine, which acts on H histamine receptors in much the same way as cimetidine despite its lack of an imidazole ring, failed to produce the same effect. On the other hand, imidazole itself was similar to cimetidine in antagonizing PE and SY induced by (±) NPA, whether injected IP or ICV. Neither imidazole nor cimetidine antagonized the stereotyped behaviour (SB) induced by (±) NPA. Indeed, imidazole reduced the latency of this response. A mechanism which may underly these effects is discussed, as well as the possible preclinical use of this test in animals. [ABSTRACT FROM AUTHOR]

Lisuride increased the incidence of stretching and yawning (SY) as well as of penile erection (PE) and elicited stereotyped behavior (SB), aggressive behavior and mounting in male rats, depending on the dose used. SY was prevented by two dopaminergic antagonists, haloperidol and sulpiride, but not by methysergide, a serotoninergic antagonist, while PE was antagonized by all three drugs. With regard to SB, aggressive behavior and mounting, all three were suppressed by haloperidol; sulpiride, while partially antagonizing aggressiveness, failed to affect SB and mounting; methysergide did not significantly influence any of the three. This suggests that lisuride principally affects the dopaminergic system. Although further detailed studies are required to elucidate which type of the complex population of DA-receptors is involved in each kind of behavior, we suggest that SY at least is due to the activation by lisuride of presynaptic DA-receptors. [ABSTRACT FROM AUTHOR]

The influence of lisuride on naloxone-induced withdrawal signs (wet shakes, escape attempts) was studied in morphine-dependent rats. Lisuride, injected IP at doses of 12.5 and 25 μg/kg, inhibited wet shakes while not significantly altering escape attempts induced by naloxone (4 mg/kg IP). At higher doses (50 and 100 μg/kg IP), lisuride's inhibitory effect on wet shakes persisted while escape attempts were actually potentiated with respect to control withdrawal rats. Increases in aggressive behavior were seen at all doses, and were dose-related. Haloperidol (0.3 mg/kg IP), administered 40 min before lisuride, did not modify the antagonistic effect on wet shakes, unlike sulpiride (40 mg/kg IP 30 min before lisuride), but at the same time blocked the increase in escape attempts and aggressiveness induced by lisuride. We suggest that lisuride modulates withdrawal signs by stimulation of dopamine receptors in the CNS. The effect of the dopamine mimetic N- n-propylnorapomorphine (NPA) on the same variables is reported as well as the influence of haloperidol on NPA, and a comparison between the effects of the two drugs is made. [ABSTRACT FROM AUTHOR]

We find and propose an explanation for a large variety of modularity-related symmetries in problems of 3-manifold topology and physics of 3d N = 2 theories where such structures a priori are not manifest. These modular structures include: mock modular forms, SL(2,ℤ) Weil representations, quantum modular forms, non-semisimple modular tensor categories, and chiral algebras of logarithmic CFTs. [ABSTRACT FROM AUTHOR]

Naloxone at a dose of 2 mg·kg, which per se did not significantly alter the copulatory pattern of sexually active adult male rats, did significantly reduce the intromission frequency as well as latency to ejaculation when administered before a low and inactive dose of N-n-propylnorapomorphine (0.5 μg·kg). [ABSTRACT FROM AUTHOR]

The importance of non-human DNA in the forensic field has increased greatly in recent years, together with the type of applications. The molecular species identification of animal and botanical material may be crucial both for wildlife trafficking and crime scene investigation. However, especially for forensic botany, several challenges slow down the implementation of the discipline in the routine.Although the importance of molecular analysis of animal origin samples is widely recognized and the same value is acknowledged to the botanical counterpart, the latter does not find the same degree of application.The availability of molecular methods, especially useful in cases where the material is fragmented, scarce or spoiled preventing the morphological identification, is not well known. This work is intended to reaffirm the relevance of non-human forensic genetics (NHFG), highlighting differences, benefits and pitfalls of the current most common molecular analysis workflow for animal and botanical samples, giving a practical guide. A flowchart describing the analysis paths, divided in three major working areas (inspection and sampling, molecular analysis, data processing and interpretation), is provided. More real casework examples of the utility of non-human evidence in forensic investigations should be shared by the scientific community, especially for plants. Moreover, concrete efforts to encourage initiatives in order to promote quality and standardization in the NHFG field are also needed. [ABSTRACT FROM AUTHOR]