Peripherality and proximity. Do business support services matter?

This essay is based on empirical evidence from the case of Tuscany (Italy) and follows previous work on the role and meaning of image in regional development and innovation policies (Bellini, 2004). Discussions about image and branding policies is usually placed in the framework of "place marketing" and marketing literature helps in defining the features, components and main characters of image and of its relationship with local identity. We suggest, however, that managing images is also a political process with significant impact in supporting and shaping the scenario (perceptions and expectations) for innovation policies. In fact this process implies a competition between images in order to "control" the representation of the past, present and future of an area. This competition aims at influencing the policy agenda by manipulating the gap between image and identity. In other words, we suggest that image-related policies should be considered part of the toolbox of a modern innovation policy.

Celecoxib inhibits proliferation and survival of chronic myelogeous leukemia (CML) cells via AMPK-dependent regulation of β-catenin and mTORC1/2.

CML is effectively treated with tyrosine kinase inhibitors (TKIs). However, the efficacy of these drugs is confined to the chronic phase of the disease and development of resistance to TKIs remains a pressing issue. The anti-inflammatory COX2 inhibitor celecoxib has been utilized as anti-tumour drug due to its anti-proliferative activity. However, its effects in hematological malignancies, in particular CML, have not been investigated yet. Thus, we tested biological effects and mechanisms of action of celecoxib in Philadelphia-positive (Ph+) CML and ALL cells.We show here that celecoxib suppresses the growth of Ph+ cell lines by increasing G1-phase and apoptotic cells and reducing S- and G2-phase cells. These effects were independent of COX2 inhibition but required the rapid activation of AMP-activated protein kinase (AMPK) and the consequent inhibition mTORC1 and 2. Treatment with celecoxib also restored GSK3β function and led to down-regulation of β-catenin activity through transcriptional and post-translational mechanisms, two effects likely to contribute to Ph+ cell growth suppression by celecoxib.Celecoxib inhibited colony formation of TKI-resistant Ph+ cell lines including those with the T315I BCR-ABL mutation and acted synergistically with imatinib in suppressing colony formation of TKI-sensitive Ph+ cell lines. Finally, it suppressed colony formation of CD34+ cells from CML patients, while sparing most CD34+ progenitors from healthy donors, and induced apoptosis of primary Ph+ ALL cells.Together, these findings indicate that celecoxib may serve as a COX2-independent lead compound to simultaneously target the mTOR and β-catenin pathways, key players in the resistance of CML stem cells to TKIs

Unusual Signs and Symptoms in HIV-Positive Patients Coinfected with Leishmania spp: The Importance of Neglected Tropical Disease in Differential Diagnosis

Leishmaniasis is a parasitic disease affecting both animals and humans, acquired with the bite of sand flies or, in Injection Drug Users (IDUs), with contaminated needles, still hypoendemic in Sicily and the Mediterranean basin. Even though it is responsible for 20,000 to 40,000 deaths per year, this parasitic infection is still considered a neglected tropical disease. People Living with HIV (PLWH) are considered at high-risk of developing Leishmaniasis and, despite the introduction of Highly Active Anti-Retroviral Therapy (HAART), mortality rate and relapses prevalence are still high in coinfected people.We present a case of HIV-Leishmania coinfection, posing the attention on the atypical signs and symptoms and the importance of thinking about other causes than the HIV infection progression when the patient presents with a worsening of his immune status during HAART

Bacteremic meningitis due to Pasteurella multocida resistant to first line antibiotic therapy

Pasteurella species reside in the gastrointestinal tract of many animals, especially in pets such as cats or dogs. Zoonotic transmission of Pasteurella to human is documented. We describe a case of meningitis in a 66-year-old woman with positive blood culture for Pasteurella multocida. Meningitis caused by zoonosis agents is a rare event, but it should be suspected in patients that have recreational or professional exposure to animals. In this case, not only the etiologic agent was rare, but the microorganism was also resistant to firstline antibiotic drugs

Correlation Between Voltage and Impedance Mapping in Patients with Atrial Fibrillation

Background. Pulmonary vein isolation (PVI) represents the cornerstone of paroxysmal (PAF) and persistent atrial fibrillation (PsAF) ablation. Impedance values provide insights on tissue conductive properties. Methods. Consecutive patients undergoing PAF and PsAF ablation were prospectively enrolled. All the patients underwent a preprocedural multidetector computed tomography (MDCT) to evaluate left atrial wall thickness (LAWT). Electroanatomic maps were acquired with the ablation catheter, and impedance values (Ω) and voltage amplitude (mV) of bipolar electrograms were collected. Results. A total of 60 patients (40 with PAF and 20 with PsAF) were included in the study. In all PAF cases, no voltage value lower than 0.5 mV was found at LA mapping; the corresponding mean impedance value was 151.5 ± 5.4 Ω. In PsAF cases, voltage values inferior to 0.05 mV have been reported in 19/20 patients. PsAF patients showed a mean impedance value of 129.1 ± 3.8 Ω. The correlation analysis between bipolar voltage and impedance reported an rs value of 0.4166 (p < 0.001), showing a positive correlation between the two variables. On the contrary, no direct correlation was found between voltage and LAWT and between impedance and LAWT (rsv-t = 0.1838; rsi-t = 0.1133, respectively). Conclusions. This research study suggests a correlation between voltage amplitude and impedance values, so that impedance might be used for arrhythmogenic substrate characterization

How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment

Low-voltage area ablation in addition to pulmonary vein isolation in patients with atrial fibrillation: a systematic review and meta-analysis

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52-0.81, p < 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] -5.32 min, 95% CI -19.01-8.46 min, p = 0.45), fluoroscopy time (MD -1.10 min, 95% CI -2.48-0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40-1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men