Search

Human regulatory T cells (T(reg) cells) that develop from conventional T cells (T(conv) cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced T(reg) cells (iT(reg) cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iT(reg) cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2-related suppressive activity of iT(reg) cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of T(reg) cells in health and in autoimmunity.

Aim: To assess the prevalence of anterior vaginal wall dehiscence in women who underwent anterior vaginal wall colpotomy for pelvic organ prolapse or stress urinary incontinence and to evaluate the influence of suture materials and techniques on wound dehiscence. Materials and Methods: This multicenter, prospective study enrolled naïve women for urogynecological surgery affected by anterior vaginal wall defect or stress urinary incontinence. Performed surgical procedures were anterior vaginal wall repair (AVWR) with native tissue (N-AVWR) or polypropylene mesh (M-AVWR), trans-obturator polypropylene in-out middle urethral sling (MUS). Used suture materials were Vicryl 2-0, Vicryl Rapide 2-0, and Monocryl 3-0. Suture techniques were running interlocking or interrupted. Follow-up was performed daily during hospitalization and in outpatient clinic after 10–14, 30 days, and after 3 months. Results: A total of 1139 patients were enrolled. AVWR were 790: 89.1% N-AVWR, and 10.9% M-AVWR. Polypropylene MUS were 349. Women with prosthetic implantation were 38.2%, while 61.8% had native tissue repair. Overall Vicryl was used in 53.9%, Vicryl Rapide in 37.4%, and Monocryl in 8.7%. Overall running interlocking sutures were 66.5%, while interrupted were 33.5%. Overall wound dehiscence prevalence was 0.9% (10/1139). Wound dehiscence rate of 0.6% (5/790) was documented in AVWR: 0.3% (2/704) in N-AVWR, and 3.5% (3/86) in M-AVWR. Among women underwent MUS, 1.4% (5/349) showed wound dehiscence. In patients who underwent prosthetic surgery, the overall dehiscence prevalence was 1.8% (8/435). A statistically significant higher rate of wound dehiscence was found in women with implanted prosthetic materials. Discussion: We reported for the first time the prevalence of wound dehiscence in females who underwent colpotomy for AVWR or MUS. Wound dehiscence occurrence was low, but non-negligible. We found that this complication was poorly associated to the suture methods and materials, while prosthetic material represented a risk factor for wound healing.

Objective: To present a retrospective analysis on the oncological and functional outcomes of a single-center experience on a large series of extraperitoneal laparoscopic radical prostatectomies (eLRP) with an extended follow-up. Materials and methods: Herein we present a retrospective review of patients who underwent eLRP. Oncological and functional follow-up data were collected by means of outpatient visits and telephone interviews, assessing overall mortality and biochemical recurrence-free survival. Patients with clinical T4 stage prostate cancer (PCa), previous surgery for benign prostatic hyperplasia (BPH), previous androgen deprivation, radiotherapy, concomitant chemotherapy and/or experimental therapies, and with insufficient follow-up data were excluded. Preoperative data recorded were age, body mass index, ultrasound prostate volume, preoperative PSA and clinical stage of PCa. Operative data (operative time, nerve sparing technique and any perioperative complication) and pathological findings were obtained by consulting the surgical and pathological reports. Oncological and functional follow-up were collected during follow-up visits and telephone interview. Results: Between January 2001 and December 2019, overall 938 eLRP were performed at our Institution. The median follow-up was 132 months. 69.7% of the patients had complete dataset. The estimated overall biochemical recurrence (BCR)-free survival was 71.4% at 5 years and 58.9% at 10 years. Cancer specific survival was 84,5%. Erectile function was preserved in the most of patients as postoperative IIEF-5 score within 12 months after surgery was > 12 in the 82.1%. About the urinary incontinence, 0.76% of the patients presented severe incontinence (continued and persistent loss of urine) and 7.0% were mildly incontinent (using up to one pad per day). Conclusions; eLRP has shown oncological and functional results comparable to other minimally invasive techniques and to open radical prostatectomy (ORP), with favorable perioperative outcomes than the open technique and a reduced complication rate.

The essay aims to focus on reception and interpretation of Dostoevsky in the thought of Luigi Pareyson (1918-1991) and his heirs, who have developed a deep and original theoretical reading of Dostoevsky's work, able to bring out not only its ethical stance, but most of the essential aspects of his thought, and to investigate its current relevance. The reflection of Pareyson – who promoted the introduction of Dostoevsky's thought into the academic circles of Turin, being convinced that philosophy cannot avoid confronting the issues it explores – consists of three main moments: the experience of good and evil, the experience of freedom and the experience of God. Starting from consideration of Dostoevsky's characters as ideas, Pareyson proposes a new and coherent philosophical interpretation of his work, which can undoubtedly be compared to those of Ivanov, Berdjaev, Evdomikov, Šestov. His observations around the Legend of the Grand Inquisitor and the "refutation of Ivan" – which, according to him, constitute the most significant and theoretically prolific moments of Dostoevsky's production – seem unaffected by the flow of time and could still represent a valuable and indispensable contribution to the understanding not only of the great Russian author, but of human nature itself.

An amendment to this paper has been published and can be accessed via the original article.

Cinnamomum verum L. essential oil (CEO), commonly known as Ceylon cinnamon or cinnamon tree, is regarded as one of the most employed essential oils in the field of aromatherapy. It is usually applied externally as astringent, antipruritic, rubefacient, and anti-septic agent. Furthermore, both in vitro and in vivo research have demonstrated its numerous pharmacological effects, including the potentiality for treating neuralgia, myalgia, headache, and migraine. Several pieces of research also corroborated its significant antiviral and antimicrobial properties. Cinnamaldehyde, eugenol, caryophyllene, cinnamyl acetate, and cinnamic acid are the most representative compounds that are generally found in greater quantities in CEO and play a pivotal role in determining its pharmacological activities. Due to the global antibiotic resistance scenario and the dwindling amount of funding dedicated to developing new antibiotics, in recent years research has concentrated on exploring specific economic approaches against microbial infections. In this context, the purpose of this study was the investigation of the synergistic antibacterial activities of commercially available and chemically characterized CEO in combination with sertraline, a selective serotonin reuptake inhibitor (SSRI), whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. In vitro effects of the titled combination were assessed toward a wide panel of both Gram-positive and Gram-negative bacteria. The antimicrobial efficacy was investigated by using the checkerboard microdilution method. The interesting preliminary results obtained suggested a synergistic effect (fractional inhibitory index, FICI < 0.5) of sertraline in combination with CEO, leading to severe growth inhibition for all bacterial species under investigation.

In a previous paper, we demonstrated the synergistic action of the anti-ischemic lubeluzole (Lube S) on the cytotoxic activity of doxorubicin (Dox) and paclitaxel in human ovarian cancer A2780 and lung cancer A549 cells. In the present paper, we extended in vitro the study to the multi-drug-resistant A2780/DX3 cell line to verify the hypothesis that the Dox and Lube S drug association may potentiate the antitumor activity of this anticancer compound also in the context of drug resistance. We also evaluated some possible mechanisms underlying this activity. We analyzed the antiproliferative activity in different cancer cell lines. Furthermore, apoptosis, Dox accumulation, MDR1 downregulation, ROS, and NO production in A2780/DX3 cells were also evaluated. Our results confirm that Lube S improves Dox antiproliferative and apoptotic activities through different mechanisms of action, all of which may contribute to the final antitumor effect. Moderate stereoselectivity was found, with Lube S significantly more effective than its enantiomer (Lube R) and the corresponding racemate (Lube S/R). Docking simulation studies on the ABCB1 Cryo-EM structure supported the hypothesis that Lube S forms a stable MDR1-Dox-Lube S complex, which hampers the protein transmembrane domain flipping and blocks the efflux of Dox from resistant A2780/DX3 cells. In conclusion, our in vitro studies reinforce our previous hypothesis for repositioning the anti-ischemic Lube S as a potentiating agent in anticancer chemotherapy.

Mosquito management programs in the urban environment of Italian cities mainly rely on larval control with conventional insecticides, primarily targeting the road drains that constitute the principal mosquito breeding sites encountered in public. The repeated utilization of synthetic insecticides may have adverse effects on non-targets and lead to resistance development issues, while the performance of biopesticides encounters limitations in field use. Botanical insecticides as single larval control agents or in binary mixtures with conventional insecticides have been extensively studied in the laboratory as an effective and eco-friendly alternative mosquito control method with promising results. The study herein concerns the investigation, for the first time under realistic conditions in the field, of the joint action of a carvacrol-rich oregano Essential Oil (EO) with two conventional insecticides, namely, the insect growth regulator diflubenzuron and the bio-insecticide Bacillus thuringiensis israelensis (B.t.i.), in road drains in Crevalcore city, Italy, against Culex pipiens and Aedes albopictus. According to the obtained results, the application of both plain EO and its mixtures with diflubenzuron and B.t.i. exerted very high efficacy in terms of immature mosquito population reduction over a two-week period. Three weeks after treatment, the performance of the oil and its mixtures diminished but remained high, while the addition of diflubenzuron potentiated the persistent action of the oil against Cx. pipiens. These findings are indicative of the potential of mixing carvacrol-rich EO with diflubenzuron and B.t.i. as an efficient eco-friendly alternative to mono-insecticide applications in road drains against Cx. pipiens and Ae. albopictus larvae.

The sterile insect technique (SIT) is a biologically based method of pest control, which relies on the mass production, sterilization, and release of sterile males of the target species. Since females can transmit viruses, it is important to develop a mass rearing system to produce a large number of males with a low presence of females. We evaluated the effects of different strains, larval diets and sexing tools on male productivity and residual female presence for the application of SIT against Aedes albopictus. Strains coming from Italy, Germany, Greece, and Montenegro, with different levels of colonization, were reared with three larval diets: IAEA-BY, BLP-B and SLP-BY. Developed pupae were sexed using two different mechanical methods: sieve or Fay-Morlan separator. The results proved that adoption of the Fay-Morlan separator increased the productivity and limited the female presence. The IAEA-BY diet showed the lowest female contamination. Strains with a high number of breeding generations showed a decreased productivity and an increased female presence. Increased female presence was found only in extensively reared strains and only when the sorting operation was conducted with sieves. We hypothesize that extensive colonization may determine a size reduction which limits the sexing tool efficiency itself.

This article presents different stories and memories of the Tina Martins Women’s Referral Center. To this end, we moved away from the qualitative studies of history and memory in organizational studies that are based on the historic turn, which aims to go beyond the production of narratives that resort to the past as a tool for reproducing the power relations of the present. A vast amount of material was compiled from observing participants, including a field notebook, event records, and photographs, and individual interviews were recorded and transcribed. The results were organized into two main thematic axes: the first presents the process that led to the Center’s foundation and the political disputes over its space, while the second addresses the meanings present in the group’s everyday life. Given the construction of diversified and procedural historical narratives, this article proposes some critical reflections on the Center’s experience that were discussed with its members, and instigates, via memories, the adoption of the historical approach to organizational studies.

O objetivo deste artigo é apresentar as diversas histórias e memórias da Casa de Referência da Mulher Tina Martins. Para isso, partiu-se dos estudos qualitativos sobre história e memória nos Estudos Organizacionais baseados na virada histórica (historic turn), a qual visa ir além da produção de narrativas que utilizam o passado como ferramenta de reprodução das relações de poder do presente. Por meio de uma observação participante, foi construído um vasto material, como um caderno de campo, registros de eventos, fotografias e entrevistas individuais gravadas e transcritas. Esses resultados foram organizados em dois percursos temáticos principais: primeiro, apresentou-se o processo de criação da Casa, envolvendo as disputas políticas pelo seu espaço. Em seguida, foram trabalhados os sentidos presentes no cotidiano do grupo. Tendo em vista a construção de narrativas históricas diversificadas e processuais, foram propostas algumas reflexões críticas sobre a experiência da Casa, discutidas junto às integrantes, instigando, por meio das memórias, trabalhos históricos no campo dos Estudos Organizacionais.

Background and aims: Prostatic urethral lift (Urolift™) is a minimally invasive technique to treat male lower urinary tract symptoms (LUTSs) due to benign prostatic hyperplasia (BPH). The aim of the present study was to assess safety and medium- to long-term outcomes in the relief of urinary symptoms. Methods: We included 35 men, affected by severe symptomatic BPH evaluated by International Prostate Symptom Score (IPSS), with normal erectile function (EF) and ejaculatory function (EjF) evaluated by the International Index of Erectile Dysfunction (IIEF-5) and Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD-SF). Exclusion criteria were prostate larger than 70 cm 3 , bladder neck sclerosis, concomitant third prostatic lobe, and/or other cervical urethral obstruction or cancer. All patients, preoperatively, performed uroflowmetry (UFM) with peak flow (Q-max) and post void residual volume (PVR), digital rectal exam, transrectal prostate ultrasound to measure prostate volume, PSA, and cystoscopy. Follow-up was scheduled at 1–3–6 months, then yearly, evaluating UFM, IPSS, IIEF-5, and MSHQ-EjD-SF. Results: All procedures were performed by a single senior surgeon and follow-up was 33.8 ± 12 months. Preoperative PSA was 0.82 ± 0.4 ng/ml and mean operative time was 19.6 ± 10 min and 3 (2–4) implants per patient were used. Parameters reported at last follow-up schedule were: Q-max increase of 68% ( p = 0.001), PVR reduction 68% ( p = 0.005), and IPSS reduction 55% ( p 45 cm 3 were aware of the possible failure.

IntroductionTo get better insight into the management of non-metastatic castration-resistant prostate cancer (M0 CRPC), in this meta-analysis and review we aimed to present an updated evaluation of the efficacy and safety of novel hormonal therapies (nHT) for M0 CRPC according to final analyses with mature overall survival (OS) and safety data.MethodsWe analyzed metastasis-free survival (MFS), OS, time to prostate-specific antigen (PSA) progression, second-line therapies data, adverse events (AEs), including all AEs, serious AEs (SAEs), AEs leading to discontinuation of trial regimen, AEs leading to death, fatigue, dizziness, cardiovascular events, and fractures; moreover, we evaluated the impact of PSA doubling time (PSA-DT), Eastern Cooperative Oncology Group (ECOG) score, use of bone-targeted therapy, lymph lodes (LN) status, and prior HT on final OS data. A comparison among the placebo arms of the included trials in terms of survival and safety profiles was assessed.ResultsAccording to the pooled analysis with updated and mature OS data, OS was significantly improved with nHT compared to placebo (hazard ratio (HR)= 0.74, 95% confidence interval (CI)= 0.66–0.84). nHT significantly improved OS over placebo across all pre-specified subgroups. Subgroup analysis revealed a greater OS benefit in patients with PSA-DT >6 months than ≤6 months (HR= 0.69 versus HR= 0.75), ECOG 0 than 1 (HR= 0.70 versus HR= 0.80), N1 disease than N0 (HR= 0.61 versus HR= 0.78), and in those receiving bone-targeted therapy (HR= 0.65 versus HR= 0.74), and a comparable OS by number of prior HT (HR= 0.75 versus HR= 0.76, for HT= 1 and ≥2); yet, differences between pre-specified subgroups were not significant (all p> 0.05). Overall, the nHT arm was significantly associated with higher rates of AEs, when compared with the placebo arm. The long-term analysis showed a worse safety profile with nHT than the interim analysis.ConclusionsAccording to final analyses, nHT have shown to improve OS over placebo in the setting of high-risk M0 CRPC. The long-term analysis showed a worse safety profile with nHT than the interim analysis, whit distinct profiles among different nHT. The lack of survival data regarding second-line therapies remains a major issue.

The main systemic therapy for the management of hormone-sensitive prostate cancer (PC) is androgen deprivation therapy (ADT), with the use of long-acting luteinizing hormone releasing-hormone (LHRH) agonists considered the main form of ADT used in clinical practice to obtain castration in PC. The concomitant administration of antiandrogens for the first weeks could reduce the incidence of clinical effects related to the testosterone flare-up in the first injection of LHRH. On the contrary, Gonadotropin Rh (GnRH) antagonists produce a rapid decrease of testosterone levels without the initial flare-up, with degarelix commonly used in clinical practice to induce castration in PC patients. Even if no long-term data are reported in terms of survival to define a superiority of GnRH or LHRH, for oncological efficacy and PC control, data from randomized clinical trials and from real-life experiences, suggest a difference in cardiovascular risk of patients starting ADT. The age-related decline in testosterone levels may represent a factor connected to the increase of cardiovascular disease risk, however, the role of ADT in increasing CV events remains controversial. For these reasons, the aim of the paper is to synthesize the difference in cardiovascular risk between LHRH and degarelix in patients undergoing ADT. A difference in cardiovascular risk could be indeed an important parameter in the evaluation of these two forms of castration therapy. The Randomized trials analyzed in this paper sustain a possible protective role for degarelix versus LHRH agonists in reducing the rate of new CV events and interventions in the short-term period. On the contrary, real-word data are contradictory in different national experiences and are strongly conditioned by huge differences between the LHRH agonists group and the degarelix group.

Background: Aedes albopictus is currently the most widespread invasive mosquito species in the world. It has paramount medical importance since females are efficient vectors of important viruses affecting humans. The development of alternative control strategies to complement control measures has become an imperative and involves the Sterile Insect Technique (SIT). Research to improve the productivity of mass-rearing, as well as the quality of mass-reared males is of essential importance for the success of SIT. Methods: This study compared the influence of three differently sized cages for Ae. albopictus mass-rearing on wing length, adult survival and egg production during 20 generations of colonization. Plexiglas cages of 40x40x40 cm (C1), 100 × 20 × 100 cm (C2) and 100 × 65 × 100 cm (C3) were loaded with equal adult density, and sex ratio of 1:1. An open source image processing and analysis programme (ImageJ) was used for the wing measurement and egg counting. Results: In all tested cages, we identified two periods separated by the generation showing the minimum value of each considered parameter (wing length, adult survival and egg production). The wing length and adult survival passed through the phases of initial decrease to about intermediate colonization time, and increased afterwards. Fecundity was steady during the first period and increased in the second one. Cage C1 demonstrated not only the best values for all parameters but also the smallest decrease in the initial phase. Recovering of the caged mosquitoes in the second half of the study was higher in cages C1 and C2, than in C3. Conclusions: C1 provided the least negative selection pressure on wing length, adult survival and egg production for reared Ae. albopictus. Anyhow, since maximising mosquito density by exploiting the minimum space is a priority in mosquito mass-rearing, C2 might be a better choice for better fitting the space of mass-rearing rooms.

ObjectiveIn 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an "accountability matrix", focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress.DesignWe searched peer-reviewed literature, conducted online searches, and contacted experts for 'grey' literature. We limited searches to documents published since December 2009 and used decision rules endorsed in earlier reviews.ResultsPolicy shifts are increasing coverage of key interventions for PWID in China, Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral treatment (ART) and opioid substitution treatment (OST) in both Vietnam and China, and a shift in Malaysia from a punitive law enforcement approach to evidence-based treatment are promising developments. The USA and Russia have had no advances on PWID access to needle and syringe programmes (NSP), OST or ART. There have also been policy setbacks in these countries, with Russia reaffirming its stance against OST and closing down access to information on methadone, and the USA reinstituting its Congressional ban on Federal funding for NSPs.ConclusionsPrevention of HIV infection and access to HIV treatment for PWID is possible. Whether countries with concentrated epidemics among PWID will meet goals of achieving universal access and eliminating new HIV infections remains unknown. As long as law enforcement responses counter public health responses, health-seeking behaviour and health service delivery will be limited.

Monitoring and diagnostics of the lifting systems in the field of rail transport play a fundamental role in order to enable it to function safely providing any deviations from the expected behaviour of the regular conditions. The transit of heavy convoys naturally tends to worsen the geometrical position and, of consequence, it is necessary to identify some monitoring techniques that allow to establish the maintenance of infrastructure in accordance with the standards UNI ISO 9927-1 and in according to ISO 12488-1 must be verify the tolerance for wheels and travel and traversing tracks; for a crane runway these are for example the span, the position and height of the rails.. Especially the ground infrastructure related to the bridge crane requires periodic checks. The purpose of this paper is to identify suitable geomatics techniques for monitoring of the runways of the bridge cranes. To achieve this aim, the paper is divided in more sections. In the first part, the paper describes the area involved in the monitoring and standards in the field of monitoring the wear of the rails. In the second part, the paper describes the criteria and regulations for checking the wear of the bridge cranes using several geomatics techniques, tool and software.

Abstract Background In countries where hepatitis B virus (HBV) is endemic, including Senegal, the World Health Organization recommends systematic HBV screening of pregnant women and vaccination at birth to prevent mother-to-child transmission (MTCT). This study investigated healthcare workers’ (HCW) knowledge and practices regarding HBV prevention and care in the rural region of Fatick in Senegal, as well as challenges they faced in implementing prevention activities related to HBV MTCT. Methods A mixed-methods survey was conducted between May–July 2017 among 112 HCW working in 15 healthcare facilities in two districts of the Fatick region using face-to-face questionnaires and semi-structured interviews. Descriptive statistics and chi-square/Mann-Whitney tests were used to analyze quantitative data, while qualitative data were analyzed thematically. Results The study population included 87 HCW in the quantitative component (83% women, median age [interquartile range, IQR] = 35 [31–40] years) and 11 in the qualitative component. A knowledge gap was observed in key areas of HBV infection: only 24, 51 and 38%, respectively, correctly reported that early HBV acquisition is associated with a high risk of developing chronic infection, that perinatal transmission is one of the main modes of HBV transmission in Senegal, and that three to four doses of HBV vaccine are required to ensure immunization in children. Despite good acceptability of systematic screening of pregnant women and vaccination at birth, only 48% of HCW mainly involved in prenatal care and 71% of those involved exclusively in vaccination routinely performed these two key interventions. HCW reported several structural barriers that may hinder their implementation: a lack of training in HBV and in counseling, poor availability of rapid diagnostic tests (RDT), high costs of both screening and treatment, a lack of adequate information on treatment options and missed opportunities for vaccination at birth. Conclusions HCW working in the Fatick region may be insufficiently trained and supported to effectively implement HBV prevention strategies. Our findings suggest an urgent need to strengthen MTCT prevention in this region, by improving HCW knowledge in key areas of HBV infection, providing RDT and antiviral treatment at low cost, and enhancing community-based interventions for the timely vaccination of newborns.

Los avances tecnológicos en materia de modelado e impresión 3D han significado un enorme impacto en las artes. Las instituciones educativas se enfrentan al desafío de incluir dicha tecnología en sus currículas, sin embargo, se encuentran sujetas a los tiempos protocolares que implican los cambios de planes de estudio.El presente trabajo se propone como objetivo demostrar que es posible la producción de la innovación pendiente a través de una instancia formativa extracurricular en modalidad b-learning. En este caso en particular, se abordó el caso de las Carreras de Licenciatura y Profesorado de grado universitario en Cerámica Industrial y Cerámica Artística de la Facultad de Artes y Diseño, de la UNCuyo, Argentina. El trabajo plantea tres ejes de innovación requeridos: Diseño tridimensional a través de software, Impresión 3D y Producción de matrices. Metodológicamente, la propuesta resuelve el primer eje a través de una propuesta educativa bimodal y la utilización de software libre. Los resultados alcanzados demuestran la posibilidad de la resolución de la problemática planteada incluso con estudiantes de escaso dominio informático y diferentes grupos etarios.

This paper presents some of the results obtained from the integrated use of 3D surveying techniques and illustrates some types of analysis and graphic representations that can be conducted and reproduced. The case study concerns the church of San Nicola in Montedoro that is one of the oldest in the city of Martina Franca in the province of Taranto (Italy) and presumably dates back to the fourteenth century. The work consists of a survey with different integrated methodologies, the creation of thematic tables all in order to allow a structural analysis.The contribution shows how this approach is not intended for a single case study, but starting from it can be extended to other contexts that present similar criticality and potential, often recurrent in the field of the survey and representation of cultural heritage.

Introduction: Surgery remains the gold standard for treatment in stable patients with penile deformity associated to Peyronie’s disease (PD). Aim: To evaluate the long-term results of plaque incision and buccal mucosa grafting (BMG), with or without additional tunica albuginea plication (TAP), in the correction of severe penile curvatures secondary to PD. Methods: 72 patients with severe curvature caused by PD, normal erections, and stable disease entered this prospective study. Preoperatively, they underwent penile duplex ultrasounds with measurement of curvature and length of affected side. All procedures were carried out by 1 surgeon. Patients were seen at 1, 3, 6, and 12 months postoperatively, then yearly. Subjective outcome was assessed by the Sexual Encounter Profile (SEP) questionnaire, and objective outcome was assessed by an intracavernous injection (ICI) test performed within the first year for evaluating penile rigidity, straightness, and length. Main Outcome Measure: Long-term outcomes include penile straightening, penile shortening, and sexual satisfaction. Results: Mean curvature was 71.32 ± 17.6° (range 40–110); 33 (45.8%) patients had a 2-sided curvature with a mean second curvature of 33.79 ± 12.2° (range 10–60). Additional TAP was needed in 60% of patients for complete straightening or graft stretching. All patients resumed unassisted intercourse 1 month after surgery; 4 (5.5%) refused follow-up, claiming excessive penile shortening. In the remaining 68, the ICI test showed no recurvature, shortening, or de novo erectile dysfunction. At mean follow-up of 62.01 ± 34.3 months (range 12–135), all were able to obtain an erection (SEP-1), 97.1% to penetrate (SEP-2), and 89.7% to successfully complete intercourse (SEP-3); 80.9% of them were satisfied with erection hardness (SEP-4) and 86.8% were overall satisfied (SEP-5), with the main reason for dissatisfaction being expectation of better length and rigidity. Conclusion: BMG, with or without TAP, provides excellent long-term results and is safe and reproducible, representing a valuable treatment option for PD, but great care should be taken in patient counseling to avoid unrealistic expectations.Cormio L, Mancini V, Massenio P. Combined Plaque Incision, Buccal Mucosa Grafting, and Additional Tunica Albuginea Plication for Peyronie’s Disease. Sex Med 2019;7:48–53. Key Words: Peyronie’s Disease, Penile Curvature, Tunica Albuginea Plication, Buccal Mucosa, Graft, Penis, Surgical Therapy

Abstract Background The growth in publically available microbiome data in recent years has yielded an invaluable resource for genomic research, allowing for the design of new studies, augmentation of novel datasets and reanalysis of published works. This vast amount of microbiome data, as well as the widespread proliferation of microbiome research and the looming era of clinical metagenomics, means there is an urgent need to develop analytics that can process huge amounts of data in a short amount of time. To address this need, we propose a new method for the compact representation of microbiome sequencing data using similarity-preserving sketches of streaming k-mer spectra. These sketches allow for dissimilarity estimation, rapid microbiome catalogue searching and classification of microbiome samples in near real time. Results We apply streaming histogram sketching to microbiome samples as a form of dimensionality reduction, creating a compressed ‘histosketch’ that can efficiently represent microbiome k-mer spectra. Using public microbiome datasets, we show that histosketches can be clustered by sample type using the pairwise Jaccard similarity estimation, consequently allowing for rapid microbiome similarity searches via a locality sensitive hashing indexing scheme. Furthermore, we use a ‘real life’ example to show that histosketches can train machine learning classifiers to accurately label microbiome samples. Specifically, using a collection of 108 novel microbiome samples from a cohort of premature neonates, we trained and tested a random forest classifier that could accurately predict whether the neonate had received antibiotic treatment (97% accuracy, 96% precision) and could subsequently be used to classify microbiome data streams in less than 3 s. Conclusions Our method offers a new approach to rapidly process microbiome data streams, allowing samples to be rapidly clustered, indexed and classified. We also provide our implementation, Histosketching Using Little K-mers (HULK), which can histosketch a typical 2 GB microbiome in 50 s on a standard laptop using four cores, with the sketch occupying 3000 bytes of disk space. (https://github.com/will-rowe/hulk).

This article examines the alterations in the forms of electoral contestation that occurred in Germany due to the Euro Crisis. The Great Recession has probably set in motion new windows of opportunity to awake the Sleeping Giant of European integration. Indeed, by increasing their entrepreneurial efforts on the EU issues, the German parties may have rendered this conflict more contentious, changing electoral behavior. To understand the nexus between the Euro Crisis and European integration politicization, this article analyzes the variations of the EU issue entrepreneurship achieved by the German parties between 2010 and 2014. Moreover, this work presents voting models, testing the fluctuations in the levels of EU issue voting. This two-step empirical research seeks to identify whether the Euro Crisis generated new entrepreneurial strategies, realigning the voters along the Pro-/-Anti-European issue dimension in Germany.

Alzheimer’s disease (AD) is a complex multi-factorial neurodegenerative disorder for which only few drugs (including donepezil, DPZ) are available as symptomatic treatments; thus, researchers are focusing on the development of innovative multi-target directed ligands (MTDLs), which could also alter the course of the disease. Among other pathological factors, oxidative stress has emerged as an important factor in AD that could affect several pathways involved in the onset and progression of the pathology. Herein, we propose a new series of hybrid molecules obtained by linking a phenothiazine moiety, known for its antioxidant properties, with N-benzylpiperidine or N-benzylpiperazine fragments, mimicking the core substructure of DPZ. The investigation of the resulting hybrids showed, in addition to their antioxidant properties, their activity against some AD-related targets, such as the inhibition of cholinesterases (both AChE and BChE) and in vitro Aβ1-40 aggregation, as well as the inhibition of the innovative target fatty acid amide hydrolase (FAAH). Furthermore, the drug-likeness properties of these compounds were assessed using cheminformatic tools. Compounds 11d and 12d showed the most interesting multi-target profiles, with all the assayed activities in the low micromolar range. In silico docking calculations supported the obtained results. Compound 13, on the other hand, while inactive in the DPPH assay, showed the best results in the in vitro antioxidant cell assays conducted on both HepG2 and SHSY-5Y cell lines. These results, paired with the low or absent cytotoxicity of these compounds at tested concentrations, allow us to aim our future research at the study of novel and effective drugs and pro-drugs with similar structural characteristics.

Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A “consensus” classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a “consensus” classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.

Rising global populations and enhanced standards of living in so-called developing countries have led to an increased demand of food, in particular meat, worldwide. While increasing the production of broiler meat could be a potential solution to this problem, broiler meat is plagued by health concerns, such as the development of antimicrobial resistance and lower meat quality. For this reason, the supplementation of poultry feed with vitamins and antioxidant compounds, such as polyphenols, has become an attractive prospect for research in this sector. Such supplements could be obtained by extraction of agricultural byproducts (in particular, grape pomaces and artichoke leaves and bracts), thus contributing to reductions in the total amount of waste biomass produced by the agricultural industry. In this review, the effects of poultry feed supplementation with bioactive extracts from grape pomace (skins and/or seeds), as well as extracts from artichoke leaves and bracts, were explored. Moreover, the various methods that have been employed to obtain extracts from these and other agricultural byproducts were listed and described, with a particular focus on novel, eco-friendly extraction methods (using, for example, innovative and biocompatible solvents like Deep Eutectic Solvents (DESs)) that could reduce the costs and energy consumption of these procedures, with similar or higher yields compared to standard methods.

Plasmonic nanostructures, featuring near infrared (NIR)-absorption, are rising as efficient nanosystems for in vitro photothermal (PT) studies and in vivo PT treatment of cancer diseases. Among the different materials, new plasmonic nanostructures based on Cu2−xS nanocrystals (NCs) are emerging as valuable alternatives to Au nanorods, nanostars and nanoshells, largely exploited as NIR absorbing nanoheaters. Even though Cu2−xS plasmonic properties are not linked to geometry, the role played by their size, shape and surface chemistry is expected to be fundamental for an efficient PT process. Here, Cu2−xS NCs coated with a hydrophilic mesoporous silica shell (MSS) are synthesized by solution-phase strategies, tuning the core geometry, MSS thickness and texture. Besides their loading capability, the silica shell has been widely reported to provide a more robust plasmonic core protection than organic molecular/polymeric coatings, and improved heat flow from the NC to the environment due to a reduced interfacial thermal resistance and direct electron–phonon coupling through the interface. Systematic structural and morphological analysis of the core-shell nanoparticles and an in-depth thermoplasmonic characterization by using a pump beam 808 nm laser, are carried out. The results suggest that large triangular nanoplates (NPLs) coated by a few tens of nanometers thick MSS, show good photostability under laser light irradiation and provide a temperature increase above 38 °C and a 20% PT efficiency upon short irradiation time (60 s) at 6 W/cm2 power density.

The worldwide scenario of antibiotic resistance and the falling number of funds for the development of novel antibiotics have led research efforts toward the study of specific cost-effective strategies aimed at discovering drugs against microbial infections. Among the potential options, drug repositioning, which has already exhibited satisfactory results in other medical fields, came out as the most promising. It consists of finding new uses for previously approved medicines and, over the years, many “repurposed drugs” displayed some encouraging in vitro and in vivo results beyond their initial application. The principal theoretical justification for reusing already existing drugs is that they have known mechanisms of action and manageable side effects. Reuse of old drugs is now considered an interesting approach to overcome the drawbacks of conventional antibiotics. The purpose of this review is to offer the reader a panoramic view of the updated studies concerning the repositioning process of different classes of non-antibiotic drugs in the antimicrobial field. Several research works reported the ability of some non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, antipsychotics, and statins to counteract the growth of harmful microorganisms, demonstrating an interesting winning mode to fight infectious diseases caused by antimicrobial resistant bacteria.

Abstract Background We explored the possibility to improve male/female separation (sexing) in Aedes albopictus by selection of two strains, one toward increasing sex dimorphism and another toward increasing protandry. In the laboratory we selected and crossed small males with large females to exploit dimorphism, and early pupating males with late pupating females to exploit protandry. Results While selection for enhanced dimorphism was not a profitable character, the selection for enhanced protandry up to F10 produced significant improvement in the time interval between male and female pupation. By collecting the pupae at 24 h from the beginning of pupation, without any sieving operation, we obtained about 28.50% of pupae (calculated in relation to the estimated initial number of first instar larvae used), vs 26.49% we had in the control strain, and, more interestingly, when checking the sex ratio of these pupae we observed a presence of females of 0.92% vs 23.02% in the control strain. We also modified our egg hatching protocol from the previous standard procedure that required keeping the eggs in the glass hatching container overnight (for about 14-16 h) to a new protocol where eggs are kept in the hatching container for 4 h in order to obtain more synchronized larvae. This was possible without any reduction in the egg hatching rate. Conclusions In Aedes albopictus it is possible to develop hyper-protandric strains useful to produce male pupae without applying other sexing systems. This represents a considerable achievement assisting the Sterile Insect Technique application, allowing improvement of the current sexing method based on mechanical separation. More investigations are under way in order to further enhance the male productivity capacity of the strain and to determine whether the selection has any impact on the male fitness parameters.

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions.

ABSTRACT Standard workflows for analyzing microbiomes often include the creation and curation of phylogenetic trees. Here we present EMPress, an interactive web tool for visualizing trees in the context of microbiome, metabolome, and other community data scalable to trees with well over 500,000 nodes. EMPress provides novel functionality—including ordination integration and animations—alongside many standard tree visualization features and thus simplifies exploratory analyses of many forms of ‘omic data. IMPORTANCE Phylogenetic trees are integral data structures for the analysis of microbial communities. Recent work has also shown the utility of trees constructed from certain metabolomic data sets, further highlighting their importance in microbiome research. The ever-growing scale of modern microbiome surveys has led to numerous challenges in visualizing these data. In this paper we used five diverse data sets to showcase the versatility and scalability of EMPress, an interactive web visualization tool. EMPress addresses the growing need for exploratory analysis tools that can accommodate large, complex multi-omic data sets.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and diabetes, is a highly prevalent emerging condition that can be optimally managed through a multidisciplinary patient-centred approach. National preparedness to address NAFLD is essential to ensure that health systems can deliver effective care. We present a NAFLD Preparedness Index for Europe. Methods: In June 2019, data were extracted by expert groups from 29 countries to complete a 41-item questionnaire about NAFLD. Questions were classified into 4 categories: policies/civil society (9 questions), guidelines (16 questions), epidemiology (4 questions), and care management (12 questions). Based on the responses, national preparedness for each indicator was classified into low, middle, or high-levels. We then applied a multiple correspondence analysis to obtain a standardised preparedness score for each country ranging from 0 to 100. Results: The analysis estimated a summary factor that explained 71.3% of the variation in the dataset. No countries were found to have yet attained a high-level of preparedness. Currently, the UK (75.5) scored best, although falling within the mid-level preparedness band, followed by Spain (56.2), and Denmark (43.4), whereas Luxembourg and Ireland were the lowest scoring countries with a score of 4.9. Only Spain scored highly in the epidemiology indicator category, whereas the UK was the only country that scored highly for care management. Conclusions: The NAFLD Preparedness Index indicates substantial variation between countries’ readiness to address NAFLD. Notably, even those countries that score relatively highly exhibit deficiencies in key domains, suggesting that structural changes are needed to optimise NAFLD management and ensure effective public health approaches are in place. Lay summary: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and diabetes, is a highly prevalent condition that can be optimally managed through a multidisciplinary patient-centred approach. National preparedness to address NAFLD is essential to allow for effective public health measures aimed at preventing disease while also ensuring that health systems can deliver effective care to affected populations. This study defined preparedness as having adequate policies and civil society engagement, guidelines, epidemiology, and care management. NAFLD preparedness was found to be deficient in all 29 countries studied, with great variation among the countries and the 4 categories studied.

BackgroundEuropean Association of Urology (EAU) guidelines recommend using risk-calculators (RCs), imaging or additional biomarkers in asymptomatic men at risk of prostate cancer (PCa).ObjectivesTo compare the performance of mpMRI, a RC we recently developed and two commonly used RC not including mpMRI in predicting the risk of PCa, as well as the added value of mpMRI to each RC.Design, Setting, and ParticipantsSingle-center retrospective study evaluating 221 biopsy-naïve patients who underwent prebiopsy mpMRI.Outcome Measurements and Statistical AnalysisPatients’ probabilities of any PCa and clinically significant PCa (csPC, defined as Gleason-Score ≥3 + 4) were computed according to mpMRI, European Randomized Study of Screening for Prostate Cancer RC (ERSPC-RC), the Prostate Biopsy Collaborative Group RC (PBCG-RC) and the Foggia Prostate Cancer RC (FPC-RC). Logistic regression, AUC, and Decision curve analysis (DCA) were used to assess the accuracy of tested models.Results and LimitationThe FPC-RC outperformed mpMRI in diagnosing both any PCa (AUC 0.76 vs 0.69) and csPCa (AUC 0.80 vs 0.75). Conversely mpMRI showed a higher accuracy in predicting any PCa compared to the PBCG-RC and the ERSPC-RC but similar performances in predicting csPCa. At multivariable analysis predicting csPCa and any PCa, the addition of mpMRI findings improved the accuracy of each calculator. DCA showed that the FPC-RC provided a greater net benefit than mpMRI and the other RCs. The addition of mpMRI findings improved the net benefit provided by each calculator.ConclusionsmpMRI was outperformed by the novel FPC-RC and showed similar performances compared to the PBCG and ERSPC RCs in predicting csPCa. The addition of mpMRI findings improved the diagnostic accuracy of each of these calculators

Background: Timely assessment of COVID-19 severity is crucial for the rapid provision of appropriate treatments. Definitive criteria for the early identification of severe COVID-19 cases that require intensive care unit admission are lacking.Methods: This was a single-center, retrospective case-control study of 95 consecutive adults admitted to the intensive care unit (cases) or a medical ward (controls) for laboratory-confirmed COVID-19. Clinical data were collected and changes in laboratory test results were calculated between presentation at the emergency department and admission. Univariate and multivariable logistic regression was performed to calculate odds ratios for intensive care unit admission according to changes in laboratory variables.Results: Of the 95 adults with COVID-19, 25 were admitted to intensive care and 70 to a medical ward after a median 6 h stay in the emergency department. During this interval, neutrophil counts increased in cases and decreased in controls (median, 934 vs. −295 × 106/L; P = 0.006), while lymphocyte counts decreased in cases and increased in controls (median, −184 vs. 109 × 106/L; P < 0.001). In cases, the neutrophil-to-lymphocyte ratio increased 6-fold and the urea-to-creatinine ratio increased 20-fold during the emergency department stay, but these ratios did not change in controls (P < 0.001 for both comparisons). By multivariable logistic regression, short-term increases in the neutrophil-to-lymphocyte ratio (OR = 1.43; 95% CI, 1.16–1.76) and urea-to-creatinine ratio (OR = 1.72; 95% CI, 1.20–2.66) were independent predictors of intensive care unit admission.Conclusion: Short-time changes in neutrophil-to-lymphocyte ratio and urea-to-creatinine ratio emerged as stand-alone parameters able to identify patients with aggressive disease at an early stage.