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Objective: To determine whether the bioactive sphingolipid sphingosine 1-phosphate (S1P) modulates cellular proliferation and synthesis of fibrotic proteins in leiomyoma differently than myometrial cells., Design: A basic science study using human leiomyoma and myometrial cells., Patient(s): Not applicable. This is an in vitro study performed on cellular models., Setting: Academic laboratory., Intervention(s): Leiomyoma and myometrial cells were treated with S1P, as well as with selective antagonists for S1P-specific G protein-coupled receptors and secondarily with inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and ezrin., Main Outcome Measure(s): The main outcome measures included cellular proliferation and fibrogenesis. Bromodeoxyuridine Cell Proliferation Assay was employed to measure deoxyribonucleic acid synthesis and proliferation, whereas western blot analysis was used to assess the expression of the fibrotic markers N-cadherin, α-smooth muscle actin, transgelin, and collagen type I alpha 1., Result(s): Sphingosine 1-phosphate stimulates cellular proliferation of leiomyoma but not myometrial cells. The mitogenic effect elicited by S1P relies on the engagement of its specific receptor S1P 2 and is mediated by ERK1/2 and ezrin activation. Furthermore, S1P exerts a profibrotic effect in a S1P-specific G protein-coupled receptor-dependent manner in leiomyoma but not myometrial cells., Conclusion(s): These results, besides extending the knowledge on the molecular mechanism underlying uterine leiomyoma development and fibrosis, demonstrate the pathogenetic role of S1P in leiomyoma and support the rationale for targeting S1P signaling pathway as innovative potential treatment., Competing Interests: Declaration of Interests M. Ro. has nothing to disclose. I.S. has nothing to disclose. M.P. has nothing to disclose. M. Ra. has nothing to disclose. L.R. has nothing to disclose. F.S. has nothing to disclose. M.F. has nothing to disclose. P.C. has nothing to disclose. F.P. reports funding from Fondi di Ateneo (ex 60%) and Fondazione Careggi, Project on Woman’s Health, for the submitted work. C.B. reports funding from Fondi di Ateneo (ex 60%) for the submitted work. C.D. reports funding from Fondi di Ateneo (ex 60%) for the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sexuality is a fundamental part of human existence and it encompasses thoughts, desires, behaviors, relationships, as well as neuropsychological and physiological components. However, sexuality in older adults is under-researched from the neuropsychological and psychophysiological perspectives and is often neglected by healthcare providers in the clinical practice. This article aims to explore the state of the art on the neuropsychology and psychophysiology of older adults' sexuality, proposing future research directions and emphasizing its significance. By summarizing current knowledge on the sexuality of younger individuals, it was possible to lay the groundwork for formulating research questions about older adults' sexuality. The implications proposed in this article will potentially impact both the scientific and also the clinical field. In fact, gaining insights on the neuropsychological and psychophysiological aspects of sexuality in healthy older adults can also shed light into those with neurocognitive disorders., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Declaration of Interests C.B. has nothing to disclose. M.R. has nothing to disclose. C.A.S. has nothing to disclose. M.Z. has nothing to disclose. L.C. has nothing to disclose. J.D. has nothing to disclose. M.-M.D. has nothing to disclose.

Objective: To create a novel, more advanced in vitro model of human endometrium, using so-called assembloids, looking to explore endometrial receptivity in adenomyosis., Design: Evaluation of assembloid responsiveness to hormonal stimulation by immunohistochemistry, enzyme-linked immunosorbent assay, and scanning electron microscopy., Setting: University-based research unit in gynecology., Patient(s): Twelve women, six of whom were affected by adenomyosis., Intervention(s): Organoids (in the form of glandular fragments) and stromal fibroblasts were collected from endometrial biopsies. The two populations were combined inside an extracellular matrix to create 3D assembloids, which were then exposed to hormonal stimulation (β-estradiol for 48 hours, followed by β-estradiol/progesterone/cyclic adenosine monophosphate for 72 hours) to mimic the window of implantation., Main Outcome Measure(s): Glycodelin, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) expression, prolactin secretion, and pinopode development., Result(s): Endometrial organoids and stromal cells were successfully isolated from women with and without adenomyosis and combined to generate the assembloid model. On stimulation, assembloids from both groups acquired a more secretory phase-like phenotype, as demonstrated by histology, and were shown to be positive for glycodelin, LIF, and HOXA10 by immunohistochemistry. Adenomyotic assembloids expressed significantly lower levels of LIF and HOXA10 within the stromal compartment after stimulation than did healthy assembloids in the same condition. Enzyme-linked immunosorbent assay revealed prolactin secretion in vitro, showing an upward trend in hormonally treated assembloids from both healthy and affected women. By scanning electron microscopy, fully formed pinopodes were discerned on the epithelial surface of healthy assembloids after stimulation, but they were absent in case of adenomyosis., Conclusion(s): Primary assembloids can be generated from endometrial biopsies from both healthy subjects and women affected by adenomyosis. These assembloids are amenable to hormonal stimulation and mimic secretory phase-specific characteristics of endometrial tissue in vivo, including glycodelin, LIF, and HOXA10 expression, and pinopode formation. Assembloids from adenomyosis appear to be less sensitive to hormonal treatment, showing reduced expression of LIF and HOXA10 in the stromal compartment and failing to form pinopodes. All in all, endometrial assembloids may serve as an advanced preclinical model of adenomyosis-related impaired endometrial receptivity, opening up new horizons in understanding and treating the condition., Competing Interests: Declaration of Interests C.A.S. has nothing to disclose. M.R. has nothing to disclose. C.B. has nothing to disclose. M.Z. has nothing to disclose. A.C. has nothing to disclose. J.D. has nothing to disclose. M.-M.D. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To explore the imaging features and the molecular characterization of adenomyosis after menopause., Study Design: An observational cross-sectional study was performed in a group of postmenopausal patients undergoing a transvaginal ultrasound (TVUS) (n = 468). Among those presenting the US criteria for adenomyosis, also confirmed by magnetic resonance imaging (MRI), previous menstrual symptoms, gynecological and obstetric history were reviewed. In a subgroup undergoing hysterectomy, uterine specimens were analyzed by histology and expression of genes implicated in the epithelial-mesenchymal transition, inflammation and fibrosis, including the sphingosine-1-phosphate (S1P) pathway, was evaluated and compared to matched non-menopausal adenomyosis specimens., Main Outcome Measures: Direct and indirect US features of adenomyosis according to Morphological Uterus Sonographic Assessment at TVUS. Molecular characterization of postmenopausal versus pre-menopausal adenomyosis samples., Results: According to TVUS and MRI, adenomyosis was identified in 49 patients (10.4 %). On US, diffuse adenomyosis was the most common phenotype, whereas internal adenomyosis with diffuse pattern and asymmetric type was the most prevalent on MRI. Molecular analysis showed that adenomyosis lesions express markers of epithelial-mesenchymal transition, inflammation and fibrosis also in postmenopausal women. By comparing the results with those from pre-menopausal samples, the expression of α smooth muscle actin (αSMA), a marker of fibrosis, was significantly greater after menopause, and altered S1P catabolism and signaling were observed., Conclusions: Adenomyosis may be identified in postmenopausal women by imaging, either TVUS or MRI, and fibrosis is one of the key features on molecular analysis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Endometriosis is a chronic gynecological syndrome characterized by endometrial cell invasion of the extra-uterine milieu, pelvic pain and infertility. Treatment relies on either symptomatic drugs or hormonal therapies, even though the mechanism involved in the onset of endometriosis is yet to be elucidated. The signaling of sphingolipid sphingosine 1-phosphate (S1P) is profoundly dysregulated in endometriosis. Indeed, sphingosine kinase (SK)1, one of the two isoenzymes responsible for S1P biosynthesis, and S1P 1 , S1P 3 and S1P 5 , three of its five specific receptors, are more highly expressed in endometriotic lesions compared to healthy endometrium. Recently, missense coding variants of the gene encoding the receptor 1 for neuropeptide S (NPS) have been robustly associated with endometriosis in humans. This study aimed to characterize the biological effect of NPS in endometriotic epithelial cells and the possible involvement of the S1P signaling axis in its action. NPS was found to potently induce cell invasion and actin cytoskeletal remodeling. Of note, the NPS-induced invasive phenotype was dependent on SK1 and SK2 as well as on S1P 1 and S1P 3 , given that the biological action of the neuropeptide was fully prevented when one of the two biosynthetic enzymes or one of the two selective receptors was inhibited or silenced. Furthermore, the RhoA/Rho kinase pathway, downstream to S1P receptor signaling, was found to be critically implicated in invasion and cytoskeletal remodeling elicited by NPS. These findings provide new information to the understanding of the molecular mechanisms implicated in endometriosis pathogenesis, establishing the rationale for non-hormonal therapeutic targets for its treatment., (© 2024 Federation of European Biochemical Societies.)

Objective: To study the molecular mechanisms responsible for fibrosis in endometriosis by investigating whether the protein expression levels of sphingosine-1-phosphate receptor 3 (S1PR3), one of the five specific receptors of the bioactive sphingolipid sphingosine-1-phosphate (S1P), correlate with fibrosis extent in endometriotic lesions and which are the cellular mechanisms involved in this process., Design: Case-control laboratory study and cultured endometriotic cells., Setting: University research institute and university hospital., Patient(s): A total of 33 women, with and without endometriosis, were included in the study., Interventions(s): Endometriotic lesions were obtained from women with endometriosis (ovarian endometrioma, n = 8; deep infiltrating endometriosis, n = 15; [urological n = 5, gastrointestinal n = 6, and posterior n = 4]) and control endometrium from healthy women, n = 10, by means of laparoscopic and hysteroscopic surgery. The expression of S1PR3 was evaluated using immunohistochemistry and the extent of fibrosis was assessed using Masson's trichrome staining. Human-cultured epithelial endometriotic 12Z cells were used to evaluate the mechanisms involved in the profibrotic effect of S1PR3 activation., Main Outcome Measure(s): The expression of S1PR3 in endometriotic lesions is positively correlated with endometriosis-associated fibrosis. In addition, S1P induced epithelial-mesenchymal transition (EMT) and fibrosis in epithelial endometriotic cells. Using RNA interference and pharmacological approaches, the profibrotic effect of S1P was shown to rely on S1PR3, thus unveiling the molecular mechanism implicated in the profibrotic action of the bioactive sphingolipid., Result(s): The protein expression levels of S1PR3 were significantly augmented in the glandular sections of endometrioma and deep infiltrating endometriosis of different localizations with respect to the control endometrium and positively correlated with the extent of fibrosis. Sphingosine-1-phosphate was shown to have a crucial role in the onset of fibrosis in epithelial endometriotic cells, stimulating the expression of EMT and fibrotic markers. Genetic approaches have highlighted that S1PR3 mediates the fibrotic effect of S1P. Downstream of S1PR3, ezrin and extracellular-signal-regulated kinases 1 and 2 signaling were found to be critically implicated in the EMT and fibrosis elicited by S1P., Conclusion(s): Sphingosine-1-phosphate receptor 3 may represent a possible innovative pharmacological target for endometriosis., Competing Interests: Declaration of Interests C.B. has nothing to disclose. M. Rossi has nothing to disclose. V.V. has nothing to disclose. M.P. has nothing to disclose. I.S. has nothing to disclose. M. Raeispour has nothing to disclose. A.M. has nothing to disclose. F.C. has nothing to disclose. P.B. has nothing to disclose. F.P. has nothing to disclose. C.D. has nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

During pregnancy and in the post-partum period, several diseases may arise or become exacerbated. Acute pancreatitis is an inflammatory disease with an increasing incidence in Western countries. The incidence of acute pancreatitis during pregnancy is not different with respect to the general population, but this incidence increases in the first 2 years after delivery. Biliary sludge and stones are the most frequent aetiologies, followed by hypertriglyceridemia. Taking care of the mother and foetus through a potentially severe disease requires a team consisting of an obstetrician, a gastroenterologist, an anaesthesiologist, and a surgeon. It is necessary to monitor the health of the foetus/child and the mother during pregnancy, childbirth, and puerperium. The management of this care depends on the systemic and local complications, the severity of the acute pancreatitis, and the trimester of pregnancy. Some diagnostic tools and many drugs are not safe for foetuses, while interventional endoscopy and surgery have limitations and can only be used after an accurate evaluation of benefit/risk ratios. Despite these limitations, maternal mortality due to acute pancreatitis is low during pregnancy, mainly thanks to multidisciplinary approaches for these patients. A careful diet to prevent obesity, alcohol abstinence, routine serum triglyceride control, and breastfeeding for at least three months may prevent acute pancreatitis during and after pregnancy.

Objectives: Efficacy and compliance of type II diabetes treatment would greatly benefit from dosage forms providing controlled release of metformin in the upper gastrointestinal tract. In this respect, the feasibility of a new system ensuring stomach-retention and personalized release of this drug at its absorption window for multiple days was investigated., Methods: The system proposed comprised of a drug-containing core and a viscoelastic umbrella-like skeleton, which were manufactured by melt-casting and 3D printing. Prototypes, alone or upon assembly and insertion into commercially-available capsules, were characterized for key parameters: thermo-mechanical properties, accelerated stability, degradation, drug release, deployment performance, and resistance to simulated gastric contractions., Results: Each part of the system was successfully manufactured using purposely-selected materials and the performance of final prototypes matched the desired one. This included: i) easy folding of the skeleton against the core in the collapsed administered shape, ii) rapid recovery of the cumbersome configuration at the target site, even upon storage, and iii) prolonged release of metformin., Conclusions: Composition, geometry, and performance of the system developed in this work were deemed acceptable for stomach-retention and prolonged as well as customizable release of metformin in its absorption window, laying promising bases for further development steps.

One-dimensional (1D) linear nanostructures comprising sp -hybridized carbon atoms, as derivatives of the prototypical allotrope known as carbyne, are predicted to possess outstanding mechanical, thermal, and electronic properties. Despite recent advances in their synthesis, their chemical and physical properties are still poorly understood. Here, we investigate the photophysics of a prototypical polyyne (i.e., 1D chain with alternating single and triple carbon bonds) as the simplest model of finite carbon wire and as a prototype of sp -carbon-based chains. We perform transient absorption experiments with high temporal resolution (<30 fs) on monodispersed hydrogen-capped hexayne H─(C≡C) 6 ─H synthesized by laser ablation in liquid. With the support of computational studies based on ground state density functional theory (DFT) and excited state time-dependent (TD)-DFT calculations, we provide a comprehensive description of the excited state relaxation processes at early times following photoexcitation. We show that the internal conversion from a bright high-energy singlet excited state to a low-lying singlet dark state is ultrafast and takes place with a 200 fs time constant, followed by thermalization on the picosecond time scale and decay of the low-energy singlet state with hundreds of picoseconds time constant. We also show that the time scale of these processes does not depend on the end groups capping the sp -carbon chain. The understanding of the primary photoinduced events in polyynes is of key importance both for fundamental knowledge and for potential optoelectronic and light-harvesting applications of low-dimensional nanostructured carbon-based materials.

Endometriosis is a benign gynecological disease affecting ∼10% of reproductive-aged women and is defined as the presence of endometrial glands and stroma outside the uterine cavity. Endometriosis can cause a variety of health problems, from pelvic discomfort to catamenial pneumothorax, but it's mainly linked with severe and chronic pelvic pain, dysmenorrhea, and deep dyspareunia, as well as reproductive issues. The pathogenesis of endometriosis involves an endocrine dysfunction, with estrogen dependency and progesterone resistance, and inflammatory mechanism activation, together with impaired cell proliferation and neuroangiogenesis. The present chapter aims to discuss the main epigenetic mechanisms related to estrogen receptors (ERs) and progesterone receptors (PRs) in patients with endometriosis. There are numerous epigenetic mechanisms participating in endometriosis, regulating the expression of the genes encoding these receptors both indirectly, through the regulation of transcription factors, and directly, through DNA methylation, histone modifications, micro RNAs and long noncoding RNAs. This represents an open field of investigation, which may lead to important clinical implications such as the development of epigenetic drugs for the treatment of endometriosis and the identification of specific and early biomarkers for the disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The interest in compact, cost-effective, and versatile accelerators is increasing for many applications of great societal relevance, ranging from nuclear medicine to agriculture, pollution control, and cultural heritage conservation. For instance, Particle Induced X-ray Emission (PIXE) is a non-destructive material characterization technique applied to environmental analysis that requires MeV-energy ions. In this context, superintense laser-driven ion sources represent a promising alternative to conventional accelerators. In particular, the optimization of the laser-target coupling by acting on target properties results in an enhancement of ion current and energy with reduced requirements on the laser system. Among the advanced target concepts that have been explored, one appealing option is given by double-layer targets (DLTs), where a very low-density layer, which acts as an enhanced laser absorber, is grown to a thin solid foil. Here we present some of the most recent results concerning the production with deposition techniques of advanced DLTs for laser-driven particle acceleration. We assess the potential of these targets for laser-driven ion acceleration with particle-in-cell simulations, as well as their application to PIXE analysis of aerosol samples with Monte Carlo simulations. Our investigation reports that MeV protons, accelerated with a ∼20 TW compact laser and optimized DLTs, can allow performing PIXE with comparable performances to conventional sources. We conclude that compact DLT-based laser-driven accelerators can be relevant for environmental monitoring., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

The optoelectronic features of 3-hydroxyflavone (3HF) self-assembled on the surface of an n-type semiconducting metal oxide (TiO 2 ) and an insulator (Al 2 O 3 ) are herein investigated. 3HF molecules use the coordinatively unsaturated metal ions present on the oxide surface to form metal complexes, which exhibit different behaviors upon light irradiation, depending on the nature of the metal ion. Specifically, we show that the photoluminescence of the surface species can be modulated according to the chemical properties of the complex ( i.e. the binding metal ion), resulting in solid-state emitters in a high quantum yield (about 15%). Furthermore, photoinduced charge injection can be promoted or inhibited, providing a multifunctional hybrid system.

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non- BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1 , 63 BRCA2 , 11 CHEK2 , 7 PALB2 , 4 ATM , 1 ERCC5 , 1 RAD51C , 1 CDH1 , 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non- BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non- BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers.

In the past, the primary approach for the treatment of endometriosis was represented by surgery; however, after the introduction of non-invasive diagnosis of endometriosis with the development of imaging technologies, medical treatment became the preferred approach, particularly in young patients. Hormonal drugs, by blocking menstruation, are the most effective for the treatment of endometriosis-related pain, independently of phenotype (ovarian, deep, or superficial endometriosis). Gonadotropin-releasing hormone analogs and oral antagonists act on hypothalamus-pituitary-ovary axis inducing iatrogenic menopause, thus reducing dysmenorrhea and all pain symptoms. The side effects, such as hot flushes and bone loss, may be reduced by an add-back therapy. However, the cost in terms of women's health remains high in view of a long-term treatment. Progestins are considered the first-line treatment, highly effective, and with reduced side effects. In addition to the well-known and largely used Norethisterone acetate and Medroxyprogesterone acetate, recently Dienogest has become one of the most used drugs in all endometriosis phenotypes for long-term treatment. Besides, Intrauterine levornogestrel or subcutaneous etonogestrel are valid alternative for long-term treatment., Competing Interests: Conflict of Interest Statement Nothing declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Acute pancreatitis (AP) caused by gallstones has an increased rate of incidence in young women in the 2 years postpartum. Middle-aged women with longer periods of breastfeeding have less hospitalization for gallbladder disease., Aim: To investigate whether breastfeeding or other variables may be associated with AP., Methods: We conducted a population-based case-control study among all Sicilian women of childbearing age, and we identified all women who delivered (2013-2016) and had AP within 2 years postpartum. We reviewed their medical records, and for each case we matched four women of the same age (± 5 years), without AP. Univariate and multivariate logistic regression was used to estimate the odds ratios (OR) with their confidence intervals (CI) to assess associations between AP and clinical determinants., Results: In the 74 women with AP and 298 controls at univariate analysis, > 6 months oral contraception history (p < 0.01; OR 3.30; 95% CI 1.33-8.16), previous biliary disease (p < 0.001; OR 5.90; 95% CI 1.98-17.57) and smoking (p = 0.035; OR 2.04; 95% CI 1.04-4.0) were predictors of AP; amenorrhea ≥ 3 months (p < 0.001; OR 0.34; 95% CI 0.19-0.59) and breastfeeding ≥ 3 months (p < 0.001; OR 0.07; 95% CI 0.03-0.14) were protective. At multivariate analysis, previous biliary disease (p = 0.011; OR 5.49; 95% CI 1.48-20.38) and breastfeeding ≥ 3 months (p < 0.001; OR 0.06; CI 95% 0.03-0.14) were associated with AP., Conclusions: Women who breastfeed for at least 3 months and do not have a history of biliary disorders have reduced risk of developing AP in the 2 years after delivery., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endometriosis is a benign uterine disorder characterized by menstrual pain and infertility, deeply affecting women's health. It is a chronic disease and requires a long term management. Hormonal drugs are currently the most used for the medical treatment and are based on the endocrine pathogenetic aspects. Estrogen-dependency and progesterone-resistance are the key events which cause the ectopic implantation of endometrial cells, decreasing apoptosis and increasing oxidative stress, inflammation and neuroangiogenesis. Endometriotic cells express AMH, TGF-related growth factors (inhibin, activin, follistatin) CRH and stress related peptides. Endocrine and inflammatory changes explain pain and infertility, and the systemic comorbidities described in these patients, such as autoimmune (thyroiditis, arthritis, allergies), inflammatory (gastrointestinal/urinary diseases) and mental health disorders.The hormonal treatment of endometriosis aims to block of menstruation through an inhibition of hypothalamus-pituitary-ovary axis or by causing a pseudodecidualization with consequent amenorrhea, impairing the progression of endometriotic implants. GnRH agonists and antagonists are effective on endometriosis by acting on pituitary-ovarian function. Progestins are mostly used for long term treatments (dienogest, NETA, MPA) and act on multiple sites of action. Combined oral contraceptives are also used for reducing endometriosis symptoms by inhibiting ovarian function. Clinical trials are currently going on selective progesterone receptor modulators, selective estrogen receptor modulators and aromatase inhibitors. Nowadays, all these hormonal drugs are considered the first-line treatment for women with endometriosis to improve their symptoms, to postpone surgery or to prevent post-surgical disease recurrence. This review aims to provide a comprehensive state-of-the-art on the current and future hormonal treatments for endometriosis, exploring the endocrine background of the disease., (© 2021. The Author(s).)

Controlled insertion of electronic states within the band gap of semiconductor nanocrystals (NCs) is a powerful tool for tuning their physical properties. One compelling example is II-VI NCs incorporating heterovalent coinage metals in which hole capture produces acceptor-bound excitons. To date, the opposite donor-bound exciton scheme has not been realized because of the unavailability of suitable donor dopants. Here, we produce a model system for donor-bound excitons in CdSeS NCs engineered with sulfur vacancies ( V S ) that introduce a donor state below the conduction band (CB), resulting in long-lived intragap luminescence. V S -localized electrons are almost unaffected by trapping, and suppression of thermal quenching boosts the emission efficiency to 85%. Magneto-optical measurements indicate that the V S are not magnetically coupled to the NC bands and that the polarization properties are determined by the spin of the valence-band photohole, whose spin flip is massively slowed down due to suppressed exchange interaction with the donor-localized electron.

Malakoplakia is a rare condition in which histiocytic cells accumulate within different organs and tissues, sometimes mimicking neoplasia. Gynecologic involvement is extremely rare and therefore may cause relevant diagnostic confusion for both clinicians and pathologists. In this paper, we described the seventh case of ovarian malakoplakia, and we reviewed the literature to compare it with the previously reported ones. Moreover, we investigated the histologic and molecular differential diagnosis of malakoplakia, with special attention to other histiocytic disorders of gynecologic interest. Finally, we discussed the most relevant points with regard to possible pathogenesis and management. Malakoplakia often represents a forgotten entity that should be remembered preoperatively, when approaching a possible gynecologic neoplasia. Moreover, it is of remarkable importance to differentiate malakoplakia from multisystem histiocytosis involving gynecologic organs. All this would prevent misdiagnosis and overtreatment of such a rare but benign condition.

Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline.

Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation., Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared., Results: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI0.17-0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR0.70; 95% CI0.44-1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR0.32; 95% CI0.13-0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00-0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11-0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02-0.38; p = 0.02)., Conclusions: In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment., Lay Summary: We aimed to determine whether direct-acting antivirals (DAAs) significantly improve overall survival in patients with hepatitis C virus-related compensated cirrhosis and a first diagnosis of hepatocellular carcinoma (HCC) which has been successfully treated with curative resection or ablation. Using propensity-score matched patients, we found that DAAs improved overall survival and reduced the risk of hepatic decompensation. However, the risk of HCC recurrence was not significantly reduced., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

"Charge engineering" of semiconductor nanocrystals (NCs) through so-called electronic impurity doping is a long-standing challenge in colloidal chemistry and holds promise for ground-breaking advancements in many optoelectronic, photonic, and spin-based nanotechnologies. To date, our knowledge is limited to a few paradigmatic studies on a small number of model compounds and doping conditions, with important electronic dopants still unexplored in nanoscale systems. Equally importantly, fine-tuning of charge engineered NCs is hampered by the statistical limitations of traditional approaches. The resulting intrinsic doping inhomogeneity restricts fundamental studies to statistically averaged behaviors and complicates the realization of advanced device concepts based on their advantageous functionalities. Here we aim to address these issues by realizing the first example of II-VI NCs electronically doped with an exact number of heterovalent gold atoms, a known p-type acceptor impurity in bulk chalcogenides. Single-dopant accuracy across entire NC ensembles is obtained through a novel non-injection synthesis employing ligand-exchanged gold clusters as "quantized" dopant sources to seed the nucleation of CdSe NCs in organic media. Structural, spectroscopic, and magneto-optical investigations trace a comprehensive picture of the physical processes resulting from the exact doping level of the NCs. Gold atoms, doped here for the first time into II-VI NCs, are found to incorporate as nonmagnetic Au + species activating intense size-tunable intragap photoluminescence and artificially offsetting the hole occupancy of valence band states. Fundamentally, the transient conversion of Au + to paramagnetic Au 2+ (5d 9 configuration) under optical excitation results in strong photoinduced magnetism and diluted magnetic semiconductor behavior revealing the contribution of individual paramagnetic impurities to the macroscopic magnetism of the NCs. Altogether, our results demonstrate a new chemical approach toward NCs with physical functionalities tailored to the single impurity level and offer a versatile platform for future investigations and device exploitation of individual and collective impurity processes in quantum confined structures.

Aim: This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients., Methods: Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months., Results: Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9-44.3). Only baseline Child-Pugh class was associated with survival., Conclusion: Sorafenib could result in long-term control of HCC in a relevant proportion of patients. Given the availability of regorafenib in the second-line setting, an earlier introduction of systemic therapy may be considered according to clinical indications.

Direct-acting antivirals (DAAs) revolutionised the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), also in more advanced patients, with a good safety profile and a proven positive effect on the reduction of risk of HCC occurrence. Nevertheless, patients with an history of successfully treated early HCC were initially excluded from pivotal trials. Although some initial retrospective studies, affected by several methodological issues, raised concerns regarding a possible harmful effect on the risk of HCC recurrence after antiviral therapy, more recent prospective studies and meta-analyses provided evidence that risk of HCC recurrence after DAA therapy is similar, or even lower, than that observed in patients treated with interferon or in DAA-untreated controls. In the future, a meta-analyses of individual patient data would be necessary to definitively close this clinical debate, as well as prospective studies assessing ‘true endpoints’, such as overall survival.

Electronic doping of colloidal semiconductor nanostructures holds promise for future device concepts in optoelectronic and spin-based technologies. Ag + is an emerging electronic dopant in III-V and II-VI nanostructures, introducing intragap electronic states optically coupled to the host conduction band. With its full 4d shell Ag + is nonmagnetic, and the dopant-related luminescence is ascribed to decay of the conduction-band electron following transfer of the photoexcited hole to Ag + . This optical activation process and the associated modification of the electronic configuration of Ag + remain unclear. Here, we trace a comprehensive picture of the excitonic process in Ag-doped CdSe nanocrystals and demonstrate that, in contrast to expectations, capture of the photohole leads to conversion of Ag + to paramagnetic Ag 2+ . The process of exciton recombination is thus inextricably tied to photoinduced magnetism. Accordingly, we observe strong optically activated magnetism and diluted magnetic semiconductor behaviour, demonstrating that optically switchable magnetic nanomaterials can be obtained by exploiting excitonic processes involving nonmagnetic impurities.

Objective: To assess whether cortical bone thickness and density vary in relation to age, sex and skeletal pattern at the maxillary and mandibular areas suitable for miniplates placement for orthodontic purposes., Materials and Methods: CBCT of 92 subjects (42 males and 50 females) with skeletal class I, II or III malocclusion, divided between adolescents and adults, were examined. InVivoDental ® software (Anatomage Inc, USA) was used to measure 34 maxillary areas and 40 mandibular areas per side. Values obtained were then compared between the groups of subjects. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney rank-sum test for independent samples., Results: No significant differences were found in the cortical bone thickness values between the three skeletal patterns, and according to sex and age. Both maxilla and mandible showed an increase in cortical bone thickness from the anterior towards the posterior regions, and from the alveolar boneto the basal bone. Cortical bone density significantly varied in relation to the subject's age, with adults always showing higher values. Slight clinically significant differences were found between the three skeletal patterns and sex., Conclusion: In terms of cortical bone thickness, age, sex and skeletal pattern do not represent valid decision criteria for the evaluation of the best insertion areas for miniplates, while in terms of cortical bone density, only age is useful as a decision criterion., (Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.)

We report the colloidal synthesis of ∼5.5 nm inverse spinel-type oxide Ga 2 FeO 4 (GFO) nanocrystals (NCs) with control over the gallium and iron content. As recently theoretically predicted, some classes of spinel-type oxide materials can be intrinsically doped by means of structural disorder and/or change in stoichiometry. Here we show that, indeed, while stoichiometric Ga 2 FeO 4 NCs are intrinsic small bandgap semiconductors, off-stoichiometric GFO NCs, produced under either Fe-rich or Ga-rich conditions, behave as degenerately doped semiconductors. As a consequence of the generation of free carriers, both Fe-rich and Ga-rich GFO NCs exhibit a localized surface plasmon resonance in the near-infrared at ∼1000 nm, as confirmed by our pump-probe absorption measurements. Noteworthy, the photoelectrochemical characterization of our GFO NCs reveal that the majority carriers are holes in Fe-rich samples, and electrons in Ga-rich ones, highlighting the bipolar nature of this material. The behavior of such off-stoichiometric NCs was explained by our density functional theory calculations as follows: the substitution of Ga 3+ by Fe 2+ ions, occurring in Fe-rich conditions, can generate free holes (p-type doping), while the replacement of Fe 2+ by Ga 3+ cations, taking place in Ga-rich samples, produces free electrons (n-type doping). These findings underscore the potential relevance of spinel-type oxides as p-type transparent conductive oxides and as plasmonic semiconductors.

Female sexual dysfunction (FSD) and quality of life (QOL) are both multidimensional and have a bidirectional relationship across the reproductive life span and beyond. Methodological difficulties exist in estimating the real prevalence of FSD because it is hard to determine the level of distress associated with sexual symptoms in a large-scale survey. Approximately 40-50% of all women report at least one sexual symptom, and some conditions associated with hormonal changes at menopause, such as vulvovaginal atrophy (VVA) and hypoactive sexual desire disorder (HSDD), have a significant impact on sexual function and QOL. Sexual distress peaks at midlife, declines with age and is strongly partner-related. Many postmenopausal women are still sexually active, especially if they are in a stable partnership. Even though sexual functioning is impaired, a variety of psychosocial factors may maintain sexual satisfaction. That being so, health care providers (HCPs) should proactively address sexual symptoms at midlife and in older women, from a balanced perspective. Adequate counselling should be offered. Women with distressing symptoms may benefit from tailored hormonal and non-hormonal therapies, whereas women without distress related to their sexual experiences should not receive any specific treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Risk-reducing salpingo-oophorectomy is the mainstay of ovarian cancer prevention in BRCA mutation carriers. However, premature menopause exerts many short and long-term consequences on the individual health that are preventable with a tailored approach. Even though our level of knowledge on BRCA1 and -2 mutation carriers is still in its infancy, the basic principles governing the management of menopausal symptomatology and the prevention of diseases should be applied, including the use of hormone replacement therapy (HRT), approximately until the age of 50. Indeed, short-term HRT significantly ameliorate quality of life and symptoms associated to vulvo-vaginal atrophy, without displaying an adverse effect on oncologic outcomes in BRCA1 and BRCA2 mutation carriers without a personal history of breast cancer. Premature menopause affects significantly also bone health, cardiovascular parameters and cognition. A standard of care is required in order to identify those women at higher risk of developing chronic conditions at midlife and beyond. Appropriate counseling on both hormonal and non-hormonal treatments is an essential part of a shared decision on the most effective management of women at high-risk for hereditary genital and breast cancer.

Two-color emitting colloidal semiconductor nanocrystals (NCs) are of interest for applications in multimodal imaging, sensing, lighting, and integrated photonics. Dual color emission from core- and shell-related optical transitions has been recently obtained using so-called dot-in-bulk (DiB) CdSe/CdS NCs comprising a quantum-confined CdSe core embedded into an ultrathick (∼7-9 nm) CdS shell. The physical mechanism underlying this behavior is still under debate. While a large shell volume appears to be a necessary condition for dual emission, comparison between various types of thick-shell CdSe/CdS NCs indicates a critical role of the interface "sharpness" and the presence of potential barriers. To elucidate the effect of the interface morphology on the dual emission, we perform side-by-side studies of CdSe/CdS DiB-NCs with nominally identical core and shell dimensions but different structural properties of the core/shell interface arising from the crystal structure of the starting CdSe cores (zincblende vs wurtzite). While both structures exhibit dual emission under comparable pump intensities, NCs with a zincblende core show a faster growth of shell luminescence with excitation fluence and a more readily realized regime of amplified spontaneous emission (ASE) even under "slow" nanosecond excitation. These distinctions can be linked to the structure of the core/shell interface: NCs grown from the zincblende cores contain a ∼3.5 nm thick zincblende CdS interlayer, which separates the core from the wurtzite CdS shell and creates a potential barrier for photoexcited shell holes inhibiting their relaxation into the core. This helps maintain a higher population of shell states and simplifies the realization of dual emission and ASE involving shell-based optical transitions.

Semiconducting nanocrystals optically active in the infrared region of the electromagnetic spectrum enable exciting avenues in fundamental research and novel applications compatible with the infrared transparency windows of biosystems such as chemical and biological optical sensing, including nanoscale thermometry. In this context, quantum dots (QDs) with double color emission may represent ultra-accurate and self-calibrating nanosystems. We present the synthesis of giant core/shell/shell asymmetric QDs having a PbS/CdS zinc blende (Zb)/CdS wurtzite (Wz) structure with double color emission close to the near-infrared (NIR) region. We show that the double emission depends on the excitation condition and analyze the electron-hole distribution responsible for the independent and simultaneous radiative exciton recombination in the PbS core and in the CdS Wz shell, respectively. These results highlight the importance of the driving force leading to preferential crystal growth in asymmetric QDs, and provide a pathway for the rational control of the synthesis of double color emitting giant QDs, leading to the effective exploitation of visible/NIR transparency windows.

Quantum dots (QDs) represent one of the most promising materials for third-generation solar cells due to their potential to boost the photoconversion efficiency beyond the Shockley-Queisser limit. Composite nanocrystals can challenge the current scenario by combining broad spectral response and tailored energy levels to favor charge extraction and reduce energy and charge recombination. We synthesized PbS/CdS QDs with different compositions at the surface of TiO2 nanoparticles assembled in a mesoporous film. The ultrafast photoinduced dynamics and the charge injection processes were investigated by pump-probe spectroscopy. We demonstrated good injection of photogenerated electrons from QDs to TiO2 in the PbS/CdS blend and used the QDs to fabricate solar cells. The fine-tuning of chemical composition and size of lead and cadmium chalcogenide QDs led to highly efficient PV devices (3% maximum photoconversion efficiency). This combined study paves the way to the full exploitation of QDs in next-generation photovoltaic (PV) devices.

CdSe/CdS dot/rods nanocrystals show interesting physical properties related to the band-alignment at the hetero-interface, which controls the band-edge electron delocalization over the rods. Here the differential transmission spectra of CdSe/CdS nanorod samples with different core sizes have been measured using excitation resonant to the core transition. The photo bleaching ratio between dot and rod transitions increases with the dot size, indicating a trend towards electron localization. This trend has been further quantified by performing effective mass calculations in which the conduction band misalignment was varied in order to reproduce the observed bleaching feature ratio. The best agreement was found for negligible conduction band misalignment for small dots of around 2.3 nm in diameter, and about -0.1 eV misalignment was estimated for the larger dots, above 3.5 nm in diameter. This shows that the band misalignment might be dependent on the geometry of the system, and we argue that this might be related to different strain developed at the hetero-interface.

The optical response of metallic nanostructures after intense excitation with femtosecond-laser pulses has recently attracted increasing attention: such response is dominated by ultrafast electron-phonon coupling and offers the possibility to achieve optical modulation with unprecedented terahertz bandwidth. In addition to noble metal nanoparticles, efforts have been made in recent years to synthesize heavily doped semiconductor nanocrystals so as to achieve a plasmonic behavior with spectrally tunable features. In this work, we studied the dynamics of the localized plasmon resonance exhibited by colloidal Cu(2-x)Se nanocrystals of 13 nm in diameter and with x around 0.15, upon excitation by ultrafast laser pulses via pump-probe experiments in the near-infrared, with ∼200 fs resolution time. The experimental results were interpreted according to the two-temperature model and revealed the existence of strong nonlinearities in the plasmonic absorption due to the much lower carrier density of Cu(2-x)Se compared to noble metals, which led to ultrafast control of the probe signal with modulation depth exceeding 40% in transmission.

Colloidal branched nanocrystals have been attracting increasing attention due to evidence of an interesting relationship between their complex shape and charge carrier dynamics. Herein, continuous wave photoinduced absorption (CW PIA) measurements of CdSe/CdS octapod-shaped nanocrystals are reported. CW PIA spectra show strong bleaching due to the one-dimensional (1D) CdS pod states (480 nm) and the zero-dimensional (0D) CdSe core states (690 nm). The agreement with previously reported ultrafast pump-probe experiments indicates that this strong bleaching signal may be assigned to state filling. Additional bleaching features at 520 and 560 nm are characterized by a longer lifetime and are thus ascribed to defect states, localized at the pod-core interface of the octapod, showing that some of the initially photogenerated carriers get quickly trapped into these long-lived defect states. However, we remark that a relevant part of electrons remain untrapped: this opens up the opportunity to exploit octapod shaped nanocrystals in photovoltaics applications, as electron acceptor materials, considering that several efficient hole extracting materials are already available for the realization of a composite bulk heterojunction., (This journal is © the Owner Societies 2011)

Background: Very few studies concern the effects of layer housing systems and age on egg technological properties. Thus the aim of this work was to study the influence of these two factors on egg performance in fresh pasta production, focusing on pasta cooking behaviour. Samples of pasta subjected to analysis were prepared with eggs laid by Hy-Line Brown hens (from 27 to 68 weeks old) housed in cage, barn and organic systems., Results: Higher average values of weight increase and matter loss during pasta cooking were observed for samples prepared with eggs laid by older hens. Such cooking behaviour indicated the development of a weaker pasta protein network, resulting from a decrease in the quantity of albumen protein and an increase in fat content, which is due to the reduction in albumen/yolk ratio during hen aging. The housing system had a significant effect only on matter loss in cooking water, but differences between samples were so small as to be unlikely perceived by consumers., Conclusion: Both hen age and housing system significantly affected pasta cooking behaviour, but the greatest effect was exerted by the hen age., (Copyright © 2010 Society of Chemical Industry.)

We studied carrier dynamics in semiconductor nanocrystals consisting of a small CdSe dot embedded in an elongated, rod-shaped CdS shell, using the ultrafast pump-probe technique. We found clear evidence of a substantial suppression of the Auger nonradiative recombination in the biexciton regime. Moreover, a simple model of the dynamics in which biexcitons show no Auger recombination, and only holes are localized in the dot, fits well the differential transmission observed at all pump densities. The long biexciton lifetime results into an observed long-living gain having a peak that is red shifted with respect to the lowest energy absorption peak. We argue that the origin of the large relative gain observed at large fillings is related to the peculiar structure of the electronic levels, and in particular, to delocalization of electrons in the rod.

Colloidal semiconductor quantum rods have demonstrated many advantageous properties as light emitters such as high quantum yield, tunable emission wavelength, and polarized emission. This makes them an interesting optical gain material for laser applications. We report room-temperature gain lifetimes in core/shell CdSe/CdS quantum rods exceeding 300 ps, and show that the long gain lifetimes result from the significant reduction of Auger recombination in our quantum rods, even though the electrons are delocalized over the rod volume. We also fabricate devices by deposition of small droplets of quantum rod solution onto flat substrates. The evaporation dynamics of the droplets are governed by the coffee stain effect which leads to the formation of well defined micron-size stripes. These stripes consist of densely packed, laterally aligned quantum rods and provide optical feedback originating from the abrupt changes of refractive index at the stripe borders. We exploit the optical gain and the coffee stain mediated self-assembly and show that we can fabricate novel microlasers solely by deposition of droplets of quantum rod solutions on flat substrates.

Nanoparticle one-dimensional photonic crystals exhibit intense, broadband reflectivity coupled with a unique mesoporosity. The latter property allows for infiltration of the one-dimensional photonic crystal with functional materials, such as emitting polymers, which in turn can lead to the fabrication of composites whereby the emitter's emission can be modulated by the photon density of states of the photonic crystal. We exploit this interaction in order to produce efficient distributed feedback lasing from a composite poly(phenylene vinylene)-infiltrated nanoparticle one-dimensional photonic crystal.

We describe an aperture scanning near-field optical microscope (SNOM) using cantilevered hollow pyramid probes coupled to femtosecond laser pulses. Such probes, with respect to tapered optical fibers, present higher throughput and laser power damage threshold, as well as greater mechanical robustness. In addition, they preserve pulse duration and polarization in the near field. The instrument can operate in two configurations: illumination mode, in which the SNOM probe is used to excite the nonlinear response in the near field, and collection mode, where it collects the nonlinear emission following far-field excitation. We present application examples highlighting the capability of the system to observe the nonlinear optical response of nanostructured metal surfaces (gold projection patterns and gold nanorods) with sub-100-nm spatial resolution.

We investigated the transient bleaching and absorption of the asymmetric core/shell CdSe/CdS nanorods using the pump-probe technique. We observed ultrafast carrier relaxation and identified hole localization dynamics with 650 +/- 80 fs time constant. Upon pumping the CdSe core, we found an intense bleaching signal in the CdS spectral region, which we assigned to the delocalization of the electronic wave function on the basis of envelope-function theoretical calculations.

The aim of this research was to study uracil and lactic and acetic acids as chemical markers for hygienic quality evaluation of raw material in liquid pasteurized egg products. Uracil, absent in sound whole eggs, was formed in raw and pasteurized egg products as a consequence of high microbial contamination (>10(6) cfu/g) after a sufficient lag time, remaining stable at 4 degrees C but disappearing after 7 days of storage at 25 degrees C. Both lactic and acetic acids, starting from initial values of 1-7 mg/kg dry matter, presented trends similar to that of uracil; however, acetic acid never decreased during the storage of raw egg products. With few exceptions, all three metabolites were produced by Enterobacter cloacae, Escherichia coli, Morganella morganii, Serratia liquefaciens, Aeromonas hydrophyla, Pseudomonas fluorescens, Enterococcus avium, and Enterococcus faecalis, separately inoculated in whole egg samples. Uracil seems to be the most sensible marker, with a suggested limit corresponding to the detectable level.

Background: Silicosis is caused by inhaling free crystalline silica. Few case reports have addressed the risk of silicosis in the jewelry trade where chalk molds containing a high percentage of silica are used in casting. We conducted a cross-sectional study involving 100 goldsmiths exposed to silica., Methods: All workers replied to a questionnaire and underwent a clinical examination, pulmonary function tests, a chest X-ray and a high-resolution CT scan., Results: High-resolution CT visualized signs of silicosis in 23 cases, confirmed by standard chest X-rays in 10. In the 23 workers with CT evidence of silicosis Total Lung Capacity, FEV1 and the Lung Diffusing Capacity did not differ from the workers without the disease. Pulmonary function tests did not correlate with silica exposure., Conclusion: In this study we demonstrate that use of chalk molds in casting in jewelry causes silicosis. The composition of the dust could be responsible of the high prevalence observed., ((c) 2007 Wiley-Liss, Inc.)

Problem: Regeneration and tolerance factor (RTF) has been recently suggested to contribute to the control of fetal-ablating immunity at the maternal-fetal interface through the induction of T helper 2 (Th2)-dominated response. The protein consists of a membrane-associated domain and an extracellular portion which is proteolitically cleaved to yield a soluble peptide. In humans, it has been shown to be expressed by invading cytotrophoblasts and decidual lymphoid cells, to be increased on peripheral blood B lymphocytes during a normal gestation and on circulating natural killer cells during unsuccessful pregnancies. However, the expression of RTF in other cell types and, specifically, in non-hematopoietic maternal cells of the human uterus has not been characterized in detail. Thus, we have specifically studied the expression and modulation of the cytokine in human endometrium obtained in different phases of the cycle and in early pregnancy., Methods: The 20 kDa extracellular domain of RTF has been localized by immunohistochemical method and Western blot analysis. Levels of RTF messenger RNA (mRNA) in basal and stimulated conditions have been evaluated by semiquantitative reverse transcription-polymerase chain reaction., Results: The extracellular domain of RTF could be detected in both the glandular epithelium and stroma with diffuse distribution in both cycling endometrium and first trimester decidua. Both cycling and pregnant endometrium expressed the gene for RTF but mRNA levels resulted significantly increased in secretory phase-endometrial stromal cells when compared to proliferative phase samples. Inflammatory cytokines, interleukin-1beta and tumour necrosis factor alpha were able to directly increase endometrial RTF mRNA expression., Conclusion: These results indicate that RTF is constitutively expressed at endometrial and decidual level and its up-regulation during the secretory phase of the cycle may be relevant in mediating some immune-related aspects of uterine physiology.