Curvature-induced stabilization and field-driven dynamics of magnetic hopfions in toroidal nanorings.

Three dimensional magnetic textures are a cornerstone in magnetism research. In this work, we analyze the stabilization and dynamic response of a magnetic hopfion hosted in a toroidal nanoring with intrinsic Dzyaloshinskii-Moriya interaction simulating FeGe. Our results evidence that unlike their planar counterparts, where perpendicular magnetic anisotropies are necessary to stabilize hopfions, the shape anisotropy originated on the torus symmetry naturally yields the nucleation of these topological textures. We also analyze the magnetization dynamical response by applying a magnetic field pulse to differentiate among several magnetic patterns. Finally, to understand the nature of spin wave modes, we analyze the spatial distributions of the resonant mode amplitudes and phases and describe the differences among bulk and surface modes. Importantly, hopfions lying in toroidal nanorings present a non-circularly symmetric poloidal resonant mode, which is not observed in other systems hosting hopfions.

Dynamic and static properties of stadium-shaped antidot arrays.

In this work we performed a detailed numerical analysis on the static and dynamic properties of magnetic antidot arrays as a function of their geometry. In particular, we explored how by varying the shape of these antidot arrays from circular holes to stadium-shaped holes, we can effectively control the magnetic properties of the array. Using micromagnetic simulations we evidenced that coercivity is very sensitive to the shape of antidots, while the remanence is more robust to these changes. Furthermore, we studied the dynamic susceptibility of these systems, finding that it is possible to control both the position and the number of resonance peaks simply by changing the geometry of the holes. Thus, this work provides useful insights on the behavior of antidot arrays for different geometries, opening routes for the design and improvement of two-dimensional technologies.

Substrates' and products' inhibition in fructanase production by a new Kluyveromyces marxianus CF15 from Agave tequilana fructan in a batch reactor.

This study focuses on fructanase production in a batch reactor by a new strain isolated from agave juice (K. marxianus var. drosophilarum) employing different Agave tequilana fructan (ATF) concentrations as substrate. The experimental data suggest that the fructanase production may be inhibited or repressed by high substrate (50 g/L) and ethanol (20.7 g/L) concentrations present in culture medium. To further analyze these phenomena an unstructured kinetic mathematical model taking into account substrate and products inhibition was proposed and fitted. The mathematical model considers six reaction kinetics and the ethanol evaporation, and predicts satisfactorily the biomass, fructan, glucose, fructose, ethanol, and fructanase behavior for different raw material initial concentrations. The proposed model is the first to satisfactorily describe the production of fructanase from branched ATF with a new strain of K. marxianus.

Disruption of adult olfactory neurogenesis induces deficits in maternal behavior in sheep.

Profound behavioral changes occur in the mother at parturition, a time when the maternal brain undergoes extensive remodeling of neural circuits, especially in olfactory structures. Adult neurogenesis, a form of brain plasticity, could constitute an adaptive response to motherhood. The present study hypothesized that chemical disruption of olfactory neurogenesis would impair the establishment of maternal behavior in sheep. In addition, because ewes are able to learn the olfactory signature of their offspring, we also examined whether disruption of olfactory neurogenesis altered recognition of the familiar lamb. At one month of gestation, ewes received either infusion of the antimitotic drug Ara-C or saline into the lateral ventricles via one-month-long osmotic minipumps. Ara-C infusion dramatically decreased olfactory neurogenesis but spared hippocampal neurogenesis. Mothers exhibiting more than a 70% reduction in olfactory neurogenesis emitted fewer maternal bleats during the first hours after parturition. Reduction of olfactory neurogenesis also negatively affected discrimination of the familiar lamb. Differences in ewes' aggressive behavior toward familiar and alien lambs were observed in sham mothers, but not in mothers with reduced olfactory neurogenesis. In addition, when ewes were given the choice between familiar and unfamiliar anesthetized lambs, so that only olfactory cues were available, mothers with a reduction in neurogenesis greater than 70% were not able to discriminate their own lamb from an alien lamb. These results indicate that adult-born olfactory neurons are to some extent involved in the establishment of maternal behavior in sheep by contributing to the processing of offspring odors.

Exposure to young preferentially activates adult-born neurons in the main olfactory bulb of sheep mothers.

New neurons are continuously added to the main olfactory bulb (MOB) of the mammalian brain. While their function has been demonstrated in olfactory learning, it is less known in an ethological context such as mothering. We addressed this question by investigating whether in sheep mothers the adult-generated olfactory neurons contribute to the processing of odors involved in attraction to lambs and in memorization of its individual signature. Parturient ewes, after having 2 days of contact with their lamb and being separated from them for 3 h, were exposed for 2 h either to their own lamb, an unfamiliar lamb or a familiar adult sheep and then sacrificed. A control group was composed of mothers not exposed to any lambs for 5 h before sacrifice. Bromodeoxyuridine, a marker of cell division, was injected 3 months before parturition and revealed through immunocytochemistry in combination with markers of activation or neuronal maturation. The percentage of adult-born cells activated in the granular layer of the MOB was compared between the four groups. Results show that the whole population of olfactory neuroblasts and in particular the 3-month-old neuroblasts, are preferentially activated by lamb exposure and that the preferential activation is specific to olfactory neurogenesis since no activation was observed in newborn neurons of the dentate gyrus. However, neither neuroblasts nor mature neurons of the MOB differentiate between familiar and unfamiliar lamb exposure. Therefore, our data shows that adult-born neurons contribute to the processing of infantile odors which are determinant for maternal behavior.

Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study.

STUDY QUESTION: Will sequential administration of highly purified (hp)-HMG after corifollitropin alfa in a GnRH antagonist protocol benefit women with poor ovarian response according to the Bologna criteria? SUMMARY ANSWER: Corifollitropin alfa followed by hp-HMG in a GnRH antagonist protocol results in very promising pregnancy rates, albeit only in young (<40 years old) poor ovarian responders fulfilling the Bologna criteria. WHAT IS KNOWN ALREADY: Poor ovarian responders fulfilling the Bologna criteria have a very poor prognosis in terms of successful IVF outcome. Although a recent study demonstrated low pregnancy rates in this group of patients after treatment with corifollitropin alfa followed by recombinant FSH in a GnRH antagonist protocol, previous studies showed that the addition of LH activity in 36- to 39-year-old women significantly increases implantation rates. STUDY DESIGN, SIZE, DURATION: In this retrospective pilot study, we included poor ovarian responders fulfilling the Bologna criteria treated with a completely novel protocol, with corifollitropin alfa followed by hp-HMG in a GnRH antagonist setting. Overall, 51 patients were treated within a period of 1 year (August 2011-August 2012). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients received 150 µg corifollitropin alfa on second day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on Day 7 of the cycle onwards. On the ninth day of the cycle, a daily fixed dose of 300 IU hp-HMG was administered until the day of ovulation triggering. The primary outcome was ongoing pregnancy rate per patient. MAIN RESULTS AND THE ROLE OF CHANCE: Among 47 eligible women, 29 patients were <40 years old and 18 patients were ≥ 40 years old. No differences were observed in endocrine profile, number of cycles with oocyte retrieval (66 versus 67%) and cycles with embryo transfer (62 versus 61%) in women <40 versus ≥ 40 years old, respectively. However, 8 of the 29 women <40 years old had an ongoing pregnancy (28%) compared with 0 of 18 patients who were ≥ 40 years of age (P = 0.017). LIMITATIONS, REASONS FOR CAUTION: Owing to the specific retrospective study design, bias cannot be ruled out and these results should not be extrapolated to other treatment protocols for poor ovarian responders. Therefore, caution should be taken when interpreting the results. WIDER IMPLICATIONS OF THE FINDINGS: The promising results from this pilot study of corifollitropin alfa followed by hp-HMG stimulation indicate a potential beneficial effect in young poor ovarian responders fulfilling the Bologna criteria. The data provide the rationale for performing a randomized controlled trial to determine if there is sound evidence for a clinical introduction of this protocol. STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest to declare. No specific funding was received for this study.

Repeated paced mating promotes the arrival of more newborn neurons in the main and accessory olfactory bulbs of adult female rats.

We have previously shown that the first-paced mating encounter increases the number of newborn cells in the granule cell layer (Gra; also known as internal cell layer, ICL) of the accessory olfactory bulb (AOB) in the adult female rat (Corona et al., 2011). In the present study we evaluated if repetition of the stimulus (paced mating) could increase the arrival of more newborn neurons in the olfactory bulb generated during the first session of paced sexual contact. Sexually naive female rats were bilaterally ovariectomized, hormonally supplemented with estradiol (E2) and progesterone (P) and randomly assigned to one of four groups: (1) without sexual contact, (2) one session of paced mating, (3) four sessions of paced mating, and (4) four sessions of non-paced mating. We also included a group of gonadally intact females. On the first day of the experiment, all females were i.p. injected with the marker of DNA synthesis bromodeoxyuridine and were killed 16 days later. Blood was collected at sacrifice to determine the plasma levels of E2 and P. The number of newborn neurons that arrived at the ICL of the AOB and the Gra of the main olfactory bulb (MOB) increased, relative to all other groups, only in the group that repeatedly mated under pacing conditions. No differences were found in E2 and P levels between supplemented groups indicating that our results are not influenced by changes in hormone concentrations. We suggest that repeated paced mating promotes the arrival of more newborn neurons in the AOB and MOB.

[Prevention of postoperative abdominal adhesions in gynecological surgery. Consensus paper of an Italian gynecologists' task force on adhesions]. / Aderenze addominali postoperatorie e loro prevenzione in chirurgia ginecologica. Documento di consenso si una "task force" di ginecologi italiani sulle aderenze.

Adhesions are the most frequent complication of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with considerable morbidity and expense, and an important mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in most patients. There is rising evidence, however, that surgeons can take important steps to reduce the impact of adhesions. A task force of Italian gynecologists with a specialist interest in adhesions having reviewed the current evidence on adhesions and considered the opportunities to reduce adhesions in Italy, have approved a collective consensus position. This consensus paper provides a comprehensive overview of adhesions and their consequences and practical proposals for actions that gynecological surgeons in Italy should take. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. They should be adopted particularly in high risk surgery and in patients with adhesiogenic conditions. Patients also need to be better informed of the risks of adhesions.

Bowel resection for deep endometriosis: a systematic review.

BACKGROUND: deep endometriosis involving the bowel often is treated by segmental bowel resection. In a recent review of over 10000 segmental bowel resections for indications other than endometriosis, low rectum resections, in particular, were associated with a high long-term complication rate for bladder, bowel and sexual function. OBJECTIVES: to review systematically segmental bowel resections for endometriosis for indications, outcome and complications according to the level of resection and the volume of the nodule. SEARCH STRATEGY: all published articles on segmental bowel resection for endometriosis identified through MEDLINE, EMBASE and ISI Web of Knowledge databases during 1997-2009. SELECTION CRITERIA: the terms 'bowel', 'rectal', 'colorectal', 'rectovaginal', 'rectosigmoid', 'resection' and 'endometriosis' were used. Articles describing more than five bowel resections for endometriosis, and with details of at least three of the relevant endpoints. DATA COLLECTION AND ANALYSIS: data did not permit a meaningful meta-analysis. MAIN RESULTS: thirty-four articles were found describing 1889 bowel resections. The level of bowel resection and the size of the lesions were poorly reported. The indications to perform a bowel resection were variable and were rarely described accurately. The duration of surgery varied widely and endometriosis was not always confirmed by pathology. Although not recorded prospectively, pain relief was systematically reported as excellent for the first year after surgery. Recurrence of pain was reported in 45 of 189 women; recurrence requiring reintervention occurred in 61 of 314 women. Recurrence of endometriosis was reported in 37 of 267 women. The complication rate was comparable with that of bowel resection for indications other than endometriosis. Data on sexual function were not found. CONCLUSIONS: after a systematic review, it was found that the indication to perform a segmental resection was poorly documented and the data did not permit an analysis of indication and outcome according to localisation or diameter of the endometriotic nodule. Segmental resections were rectum resections in over 90%, and the postoperative complication rate was comparable with that of resections for indications other than endometriosis. No data were found evaluating sexual dysfunction.

Laparoscopic sacrocolpopexy.

Laparoscopy offers great exposure and surgical detail, reduces blood loss and the need for excessive abdominal packing-- and bowel manipulation making it an excellent modality to perform pelvic floor surgery. Laparoscopic repair of level I or apical vaginal prolapse may be challenging, due to the need for extensive dissection and advanced suturing skills. However, it offers the efficacy of open abdominal sacrocolpopexy, such as lower recurrence rates and less dyspareunia-- than sacrospinous fixation, as well as the reduced morbidity of a laparoscopic approach.

[Laparoscopic approach in the pelvic floor surgery]. / Technika laparoskopického prístupu v pánevní chirurgii.

Laparoscopy offers great exposure and surgical detail, reduces blood loss and the need for excessive abdominal packing and bowel manipulation making it an excellent modality to perform pelvic floor surgery. Laparoscopic repair of level I or apical vaginal prolapse may be challenging, due to the need for extensive dissection and advanced suturing skills. However it offers the efficacy of open abdominal sacrocolpopexy, such as lower recurrence rates and less dyspareunia than sacrospinous fixation, as well as the reduced morbidity of a laparoscopic approach.

Evidence that cervical cancer cells secrete IL-2, which becomes an autocrine growth factor.

We present evidence that cervical cancer cells express a functional IL-2 receptor (IL-2R). In fact, by RT-PCR we obtained that the IL-2R is present in CALO, and INBL cells, and that it consisted of the alphaIL-2R, betaIL-2R, and gammaIL-2R chains. We also found that IL-2 is a growth factor for these cell lines, and unexpectedly that CALO and INBL themselves being cancer cells produce, and secrete IL-2. Antibodies against the alpha and beta subunits of the IL-2R inhibited cell proliferation thus hinting to a cell growth dependency on this factor. Our results thus provide evidence that the IL-2R on cervical cancer cells is part of an autocrine mechanism for its growth to the extent that, like lymphocytes, they produce and become partially dependent on this growth factor. We think that in view of our results caution should be taken when IL-2 is being considered for cancer therapy; in particular when the patient's cancer cells present the IL-2R, because as indicated by our results, the use of this factor could promote tumor growth. Finally, the possible implications of the expression of both IL-2, and IL-2R on cervical cancer cells on the immune escape mechanism of tumor cells are discussed.

Accident analysis: factors contributing to a ureteric injury during deep endometriosis surgery.

OBJECTIVE: To analyse factors associated with a ureteric injury. DESIGN: Retrospective accident analysis. SETTING: Deep endometriosis surgery in a tertiary referral centre. SAMPLE: Video recording of a surgical accident was analysed by six gynaecologists. METHODS: A 26-year-old woman underwent laparoscopy for deep endometriosis that involves the rectosigmoid and left ureter. Post operatively left ureter transection was identified and corrected by laparoscopy. Interventions were recorded and reviewed independently. MAIN OUTCOME MEASURES: Changes in surgical behaviour that could be measured were identified using the video recording. Results During the intervention, the periods of uncontrolled bleeding (P < 0.0001) and the duration of laser activation (P = 0.013) increased progressively. Simultaneous laser activation and bipolar coagulation only occurred at the end of surgery (seven episodes). Fatigue could not be measured. CONCLUSION: Unconscious acceleration of surgery, possibly as a consequence of fatigue, is suggested as a contributing factor for an error of judgement.

[Importance of microlithiasis in testicular germ cell tumor ultrasound]. / Importancia de microlitiasis en ultrasonido de neoplasias de células germinales de testículo.

INTRODUCTION: Testicular microlithiasis (TM) is an infrequent finding in testicular ultrasound and its clinical importance has not been completely defined. We analyzed the ultrasounds of patients with testicular germ cell tumors in order to analyze the correlation between TM, histological findings and clinical variables. METHODS AND MATERIALS: Fifty-seven patients with germ cell tumors and radical orchiectomy were included. Clinical, pathological, and echographic data were analyzed. RESULTS: TM was observed in 27 men (48.27%) and was absent in 30 (52.6%). Patients with TM had a greater likelihood of nonseminomatous germ cell tumors (NSGCT) vs seminomatous (55.6% vs 30%, p=0.05), stage II/III testicular cancer (51.8% vs 16.7%, p=0.005), positive surgical margins (18.5% vs 0%, p=0.021), and spermatic cord invasion (14.8% vs 0%, p=0.048). No significant difference was found in respect to other histopathological variables. CONCLUSION: This study showed that TM in testicular tumors is associated to NSGCT, advanced clinical stage, positive surgical margins, and spermatic cord invasion.

Importancia de microlitiasis en ultrasonido de neoplasias de células germinales de testículo / Importance of microlithiasis in testicular germ cell tumor ultrasound

Introducción: La microlitiasis testicular (MT) es un hallazgo poco frecuente en el ultrasonograma cuyo significado clínico no se ha definido. El presente estudio se realizó en pacientes con tumores de células germinales de testículo para analizar la relación entre MT, los hallazgos histológicos y las variables clínicas. Material y métodos: Se incluyeron 57 pacientes sometidos a orquiectomía radical por neoplasia testicular germinal y se revisaron las variables clínico patológicas y ultrasonográficas. Resultados: Hubo 30 hombres (52,6%) sin MT y 27 hombres con MT (48,27%). Los pacientes con MT tuvieron mayor proporción de tumor germinal no seminomatoso (TGNS, 55,6% vs 30%, p=0,05),de cáncer testicular estadio II/III (51,8% vs 16,7%, p=0,005), de borde quirúrgico positivo (18,5% vs0%, p=0,021) y de invasión al cordón espermático (14,8% vs 0%, p=0,048). No se encontró diferencia significativa en relación a otras variables histopatológicas. Conclusión: En este estudio se demostró una asociación entre MT en tumores testiculares con el hallazgo de TGNS, estadio clínico avanzado, borde quirúrgico positivo e invasión al cordón (AU)

Introduction: Testicular microlithiasis (TM) is an infrequent finding in testicular ultrasound and its clinical importance has not been completely defined. We analyzed the ultrasounds of patients with testicular germ cell tumors in order to analyze the correlation between TM, histological findings and clinical variables. Methods and materials: Fifty-seven patients with germ cell tumors and radical orchiectomy were included. Clinical, pathological, and echographic data were analyzed. Results: TM was observed in 27 men (48.27%) and was absent in 30 (52.6%). Patients with TM had a greater likelihood of non seminomatous germ cell tumors (NSGCT) vs seminomatous (55.6% vs 30%,p=0.05), stage II/III testicular cancer (51.8% vs 16.7%, p=0.005), positive surgical margins (18.5% vs0%, p=0.021), and spermatic cord invasion (14.8% vs 0%, p=0.048). No significant difference was found in respect to other histopathological variables. Conclusion: This study showed that TM in testicular tumors is associated to NSGCT, advanced clinical stage, positive surgical margins, and spermatic cord invasion (AU)

Three-point checklist of dermoscopy: an open internet study.

BACKGROUND: In a pilot study, the three-point checklist of dermoscopy has been shown to represent a valid and reproducible tool with high sensitivity for the diagnosis of skin cancer in the hands of a small group of nonexperts. OBJECTIVES: To re-evaluate these preliminary results in a large number of observers independently from their profession and expertise in dermoscopy. METHODS: The study was conducted via the internet to provide worldwide access for participants. After a short web-based tutorial, the participants evaluated dermoscopic images of 165 (116 benign and 49 malignant) skin lesions (15 training and 150 test lesions). For each lesion participants scored the presence of the three-point checklist criteria (asymmetry, atypical network and blue-white structures). Kappa values, odds ratios, sensitivity, specificity and likelihood ratios were estimated. RESULTS: Overall, 150 participants joined the study. The three-point checklist showed good interobserver reproducibility (kappa value: 0.53). Sensitivity for skin cancer (melanoma and basal cell carcinoma) was 91.0% and this value remained basically uninfluenced by the observers' professional profile. Only 20 participants lacking any experience in dermoscopy performed significantly more poorly, but the sensitivity was still remarkably high (86.7%) when considering that they were untrained novices in dermoscopy. The specificity was 71.9% and was significantly influenced by the profession, with dermatologists performing best. CONCLUSIONS: Our study confirms that the three-point checklist is a feasible, simple, accurate and reproducible skin cancer screening tool.

Circulating CD8+ lymphocytes, white blood cells, and survival in patients with mycosis fungoides.

BACKGROUND: There is a need for reliable, easily measurable laboratory markers that may help dermatologists to predict the course of mycosis fungoides (MF) when they first evaluate their patients. OBJECTIVES: Our objective was to identify clinical, haematological or immunological parameters as predictors of mortality in patients with MF. METHODS: We conducted a retrospective study on a prevalent cohort of 124 patients with MF hospitalized at IDI-IRCCS, Rome, Italy, from 1983 to 2001. We calculated the proportion of patients surviving (Kaplan-Meier product-limit estimates) 5 and 10 years after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. RESULTS: Patients' survival was linked to age and staging (lower survival in older patients and in patients with staging IIB-IV). Higher numbers of white blood cells (WBC) and neutrophils, lower numbers of CD8+ lymphocytes, low haematocrit and lower levels of albumin were significantly associated with a lower survival probability. When simultaneously accounting for age and staging, CD8+ [HR = 3.02, 95% confidence interval (CI) 1.01-9.07 for CD8+ < 250 vs. > or = 600 cells microL(-1)] and WBC (HR = 2.59, 95% CI 0.96-6.96 for WBC > or = 9000 vs. < 6000 cells microL(-1)) were associated with survival. In addition, we observed an exceedingly high risk of death (HR = 12.40, 95% CI 3.11-49.43) for patients with a combination of WBC > or = 9000 and CD8+ < 600 cells microL(-1) vs. WBC < 9000 and CD8+ > or = 600 cells microL(-1)). CONCLUSIONS: The measurement of CD8+ cells and WBC in MF seems to be a promising criterion to predict survival, and possibly to support treatment decisions and inclusion of patients in randomized controlled trials.

Characterization of the ultraviolet B and X-ray response of primary cultured epidermal cells from patients with disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is the most common porokeratosis and is characterized by multiple keratotic lesions which tend to occur at sun-exposed sites. A mild hypersensitivity to X-rays has been reported for DSAP-derived fibroblasts and frequent over-expression of p53 has been found in lesional epidermis. OBJECTIVES: In order to clarify whether genome maintenance mechanisms might be compromised in this disease the following approaches were undertaken: (i) primary cultured keratinocytes and fibroblasts from DSAP patients were characterized for ultraviolet (UV) B and X-ray response; (ii) 15 lesions were studied for p53 mutations, and (iii) the differentiation status of DSAP-derived keratinocytes was evaluated. METHODS: Primary cultures of keratinocytes and fibroblasts were established from lesional and nonlesional skin biopsies of two subjects with DSAP. p53 mutations were analysed by DNA sequencing of the conserved region of the TP53 gene. Differentiation was evaluated both in stratified epithelial sheets from confluent keratinocyte cultures and in organotypic skin cultures. RESULTS: The cytotoxic and apoptotic response to UVB or X-irradiation was similar in DSAP-derived keratinocytes and fibroblasts when compared with normal cells. Two of 15 lesions examined presented p53 mutations located at nondipyrimidine sites. A strikingly decreased expression of filaggrin was observed both in reconstructed epidermis and in reconstructed skin. CONCLUSIONS: The UVB and X-ray response of DSAP-derived keratinocytes and fibroblasts indicates that the actinic character of this skin pathology is not due to radiation hypersensitivity. In agreement with this finding, mutations in the p53 gene, which are often associated with UV-related skin carcinogenesis, were rarely detected in DSAP lesions and were not UV-specific. Reconstructed epidermis and reconstructed skin models successfully reproduced the main features of this genodermatosis, showing that DSAP-derived keratinocytes bear an inherent defect in the terminal differentiation programme.