Karst geomorphology of the “Canale di Pirro” polje, Apulia (Southern Italy).

In karst environment, a geomorphological map is a powerful instrument, which play a crucial role in understanding earth surface processes and landscape evolution. Furthermore, it could be very useful for speleological perspectives, natural resources exploitation and geo-hazards management (flood, sinkhole, subsidence, etc.), providing useful information that enhance the knowledge of the territory. In this work, we present a geomorphological map of the polje of “Canale di Pirro”, sited in the central part of Apulia Region, in Southern Italy, among the most interesting karst lands in the Mediterranean area. The map covers150km2withanelevationrangeof100-450ma.s.l.Thisareaisoneofthemostremarkablekarstlandforms in the region, characterized underground by a very interesting system of caves, that reaches the water table at a depth of -264 meters. The karst system, known as “Inghiottitoio di Masseria Rotolo”, following scuba-diving exploration below the watertable, has become with a depth of 324m, the deepest known cave in Apulia. The polje is bounded on both sides by tectonically-controlled ridges, showing an overall length of some 12 km. In ancient maps, dating back to the 16th century, the area is represented as crossed by a long river, called Cana. The map obtained derives from the integration of interpretation of aerial photographs, analysis of a digital elevation model and field surveys in order to obtain a correct distribution of landforms and fluvial processes, such as different varieties of karst depressions, conical hills, erosional gullies, alluvial fans and tectonic structures. It provides relevant information about the surface drainage processes, and for understanding, among other things, the groundwater circulation and the related recharge processes. This geomorphological map is part of a wider project, that combined geological, hydrogeological research and chemical analyses of the groundwater. It provides support to the ongoing studies of this part of Apulia region aimedto betterunderstand thegeological processes that originatedthe polje and its later evolution, and the related underground cave system. Further, it might also suggest possible improvements in land management and in the future choice of useful tools for the control of the quality and quantity of karst groundwater

Droplets generated from toilets during urination as a possible vehicle of carbapenem-resistant Klebsiella pneumoniae

BACKGROUND: In the health care setting, infection control actions are fundamental for containing the dissemination of multidrug-resistant bacteria (MDR). Carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (CR-KP), can spread among patients, although the dynamics of transmission are not fully known. Since CR-KP is present in wastewater and microorganisms are not completely removed from the toilet bowl by flushing, the risk of transmission in settings where toilets are shared should be addressed. We investigated whether urinating generates droplets that can be a vehicle for bacteria and explored the use of an innovative foam to control and eliminate this phenomenon. METHODS: To study droplet formation during urination, we set up an experiment in which different geometrical configurations of toilets could be reproduced and customized. To demonstrate that droplets can mobilize bacteria from the toilet bowl, a standard ceramic toilet was contaminated with a KPC-producing Klebsiella pneumoniae ST101 isolate. Then, we reproduced urination and attached culture dishes to the bottom of the toilet lid for bacterial colony recovery with and without foam. RESULTS: Rebound droplets invariably formed, irrespective of the geometrical configuration of the toilet. In microbiological experiments, we demonstrated that bacteria are always mobilized from the toilet bowl (mean value: 0.11 ± 0.05 CFU/cm2) and showed that a specific foam layer can completely suppress mobilization. CONCLUSIONS: Our study demonstrated that droplets generated from toilets during urination can be a hidden source of CR-KP transmission in settings where toilets are shared among colonized and noncolonized patients

Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia

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Linking surgical specimen length and examined lymph nodes in colorectal cancer patients.

AbstractAimThe number of examined lymph nodes (NLN) was associated with survival of stages II and III colorectal cancer (CRC) patients. Guidelines recommend examining at least 12 lymph nodes. This study investigated the influence of surgical specimen length on lymph node harvest and compliance with international guidelines.Materials and methodsThis population-based study included 4,724 cases of surgically treated CRC that were diagnosed from 2002 to 2008. Multivariate analyses were performed for the main study variables (age, gender, diagnosis at screening or in symptomatic patients, cancer site, staging, grading, number of positive nodes, neo-adjuvant treatment for rectal cancer, hospital were surgery was performed). Fractional polynomial models investigated the relationship between continuous variables and outcomes.ResultsThe NLN increased over time reaching ≥12 NLN in 64% of cases at the end of the study period. More NLN were associated with young age, right colon cancer, pT3–T4 disease, stages II and III and high grade. Fewer NLN were associated with short surgical specimen length and neo-adjuvant treatment in rectal cancer patients. Use of laparoscopy increased sharply over time.ConclusionsNLN increased over time in accordance with international guidelines. Surgical specimen length correlated with NLN which may determine therapeutic choices, particularly in stage II colon cancer. When harvested lymph nodes are under 10 in number and all are negative, chemotherapy is always recommended. As specimen lengths <20 cm were associated with a high risk of inadequate NLN counts, patients are at risk of over-treatment

Parp inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective (Review)

Epithelial ovarian cancer (EOC) has a poor prog- nosis. Since the introduction of paclitaxel as antineoplastic agent &gt;20 years ago, only a few phase III randomized trials have shown challenging data regarding different therapeutic options for facing its aggressive clinical course and granting active therapies to patients. Different studies have shown the utility of poly(ADP-ribose) polymerase (PARP) inhibitors in women with EOC with or without BRCA mutations, both germ- line and somatic. Three PARP inhibitors, olaparib, rucaparib and niraparib, have been recently approved by the Food and Drug Administration for clinical use in EOC patients, though with different clinical indications and profiles of toxicity, while two other molecules, veliparib and talazoparib, are still under clinical investigation. The aim of the present paper is to evaluate the current status of PARP inhibitors in terms of molecular activity, pharmacodynamic properties and clinical applications

Management of chronic lymphocytic leukemia: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation.

The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of chronic lymphocytic leukemia (CLL). METHODS: Key questions in the management of patients with CLL were formulated by an Advisory Committee and approved by an Expert Panel of eight senior hematologists. After a systematic review of the literature, recommendations for disease-specific and supportive therapies were formulated and graded according to the supporting evidence. Explicit consensus methods were used for providing recommendations for questions with incomplete or potentially biased evidence. RESULTS: It is recommended that therapy is commenced in patients with CLL when at least one of the following are present: B-symptoms, progressive/obstructive lymphadenopathy or organomegaly, rapid lymphocyte doubling time, anemia or thrombocytopenia (of new onset, worsening or steroid-resistant). It is recommended that patients without co-morbidity should receive fludarabine plus cyclophosphamide, whereas elderly patients with co-morbidity should receive oral chlorambucil. Younger patients with unfavorable biological risk factors should be considered for high-dose chemotherapy and autologous or allogeneic stem cell transplantation within approved clinical trials. Patients either relapsing rapidly after, or non-responsive to, first-line chlorambucil should receive fludarabine-containing regimens. Patients either relapsing soon after or not responding to fludarabine-based chemotherapy should be considered for schedules including non-cross-reactive agents, such as alemtuzumab, possibly followed by high-dose chemotherapy and autologous transplantation in the context of a clinical trial or by allogeneic stem cell transplantation. CONCLUSIONS: We describe the results of a systematic literature review and an explicit approach to consensus techniques which resulted in recommendations for the key therapeutic decisions in patients with CLL

Consensus conference on the management of tumor lysis syndrome.

Tumor lysis syndrome is a potentially life threatening complication of massive cellular lysis in cancers. Identification of high-risk patients and early recognition of the syndrome is crucial in the institution of appropriate treatments. Drugs that act on the metabolic pathway of uric acid to allantoin, like allopurinol or rasburicase, are effective for prophylaxis and treatment of tumor lysis syndrome. Sound recommendations should regulate diagnosis and drug application in the clinical setting. The current article reports the recommendations on the management of tumor lysis syndrome that were issued during a Consensus Conference project, and which were endorsed by the Italian Society of Hematology (SIE), the Italian Association of Pediatric Oncologists (AIEOP) and the Italian Society of Medical Oncology (AIOM). Current concepts on the pathophysiology, clinical features, and therapy of tumor lysis syndrome were evaluated by a Panel of 8 experts. A consensus was then developed for statements regarding key questions on tumor lysis syndrome management selected according to the criterion of relevance by group discussion. Hydration and rasburicase should be administered to adult cancer patients who are candidates for tumor-specific therapy and who carry a high risk of tumor lysis syndrome. Cancer patients with a low-risk of tumor lysis syndrome should instead receive hydration along with oral allopurinol. Hydration and rasburicase should also be administered to patients with clinical tumor lysis syndrome and to adults and high-risk children who develop laboratory tumor lysis syndrome. In conclusion, the Panel recommended rasburicase for tumor lysis syndrome prophylaxis in selected patients based on the drug efficacy profile. Methodologically rigorous studies are needed to clarify its cost-effectiveness profile

A diamond detector based dosimetric system for instantaneous dose rate measurements in FLASH electron beams

Objective. A reliable determination of the instantaneous dose rate (I-DR) delivered in FLASH radiotherapy treatments is believed to be crucial to assess the so-called FLASH effect in preclinical and biological studies. At present, no detectors nor real-time procedures are available to do that in ultra high dose rate (UH-DR) electron beams, typically consisting of μs pulses characterized by I-DRs of the order of MGy/s. A dosimetric system is proposed possibly overcoming the above reported limitation, based on the recently developed flashDiamond (fD) detector (model 60025, PTW-Freiburg, Germany). Approach. A dosimetric system is proposed, based on a flashDiamond detector prototype, properly modified and adapted for very fast signal transmission. It was used in combination with a fast transimpedance amplifier and a digital oscilloscope to record the temporal traces of the pulses delivered by an ElectronFlash linac (SIT S.p.A., Italy). The proposed dosimetric systems was investigated in terms of the temporal characteristics of its response and the capability to measure the absolute delivered dose and instantaneous dose rate (I-DR). A ‘standard’ flashDiamond was also investigated and its response compared with the one of the specifically designed prototype. Main results. Temporal traces recorded in several UH-DR irradiation conditions showed very good signal to noise ratios and rise and decay times of the order of a few tens ns, faster than the ones obtained by the current transformer embedded in the linac head. By analyzing such signals, a calibration coefficient was derived for the fD prototype and found to be in agreement within 1% with the one obtained under reference 60Co irradiation. I-DRs as high as about 2 MGy s−1 were detected without any undesired saturation effect. Absolute dose per pulse values extracted by integrating the I-DR signals were found to be linear up to at least 7.13 Gy and in very good agreement with the ones obtained by connecting the fD to a UNIDOS electrometer (PTW-Freiburg, Germany). A good short term reproducibility of the linac output was observed, characterized by a pulse-to-pulse variation coefficient of 0.9%. Negligible differences were observed when replacing the fD prototype with a standard one, with the only exception of a somewhat slower response time for the latter detector type. Significance. The proposed fD-based system was demonstrated to be a suitable tool for a thorough characterization of UH-DR beams, providing accurate and reliable time resolved I-DR measurements from which absolute dose values can be straightforwardly derived

Fertility Counseling Pattern over Time in Young Patients with Breast Cancer: A Retrospective Analysis at a Large Comprehensive Cancer Center

Background: One main issue to be considered in young patients diagnosed with early breast cancer (BC) is the impact of oncological treatments on fertility and future chances of conception. Current guidelines recommend a comprehensive addressing of oncofertility as part of the management of premenopausal BC patients, including counselling on available assisted reproduction technologies and fertility preservation (FP) strategies. The COVID-19 pandemic represented a potential hurdle to the integration of these procedures into clinical practice. This study aims to describe the time-related evolution in addressing oncofertility issues. Methods: This retrospective mono-institutional observational study considered 206 patients who received neoadjuvant chemotherapy, adjuvant chemotherapy (CT) or adjuvant endocrine therapy (ET), diagnosed with breast cancer at the age of 40 or younger in the years 2014-2015 and 2020-2021. Timerelated evolution in addressing oncofertility during oncological consultations and adoption of a fertility or ovarian function preservation (OFP) method were analyzed comparing the two different timeframes. Results: Comparing the two cohorts 2014-2015 and 2020-2021, we found a significant difference in the presence of fertility discussion records (37.4% vs 57.9%, p < 0.01), and in the application of OFP/FP techniques (54.5 vs 78.5%, p < 0.01). In the two cohorts there was a significant difference in OFP (57.6% vs 70%, p = 0.03) and FP techniques application rates (5.1% vs 19.6%, p < 0.01). In the study population, age at diagnosis resulted to influence clinicians' approach towards counseling and/or OFP/FP strategies (87.3% in patients <35 years old (yo) vs 56.7% in older patients, p < 0.01). In the 2020-2021 cohort, age resulted less influential in the choice of using an OFP/FP strategy (87% vs 72.1%, p = 0.18). A higher rate of documented fertility discussion and/or OFP/FP techniques application was recorder in patients who had not had children before BC diagnosis (80.6% vs 64.5%, p = 0.02). When considering only the 2020-2021 timeframe, parity no longer significantly affected the prescription of an OFP/FP strategy (80.4% vs 78.3%, p = 0.93). Conclusions: This study on real world data demonstrates the progressive evolution in the way clinicians approach oncofertility issues, showing a greater attention across years, with more BC patients receiving a dedicated counseling, despite the COVID-19 pandemic

Aquaporin 9 contributes to the maturation process and inflammatory cytokine secretion of murine dendritic cells

Dendritic cells (DCs) are the most potent antigen-presenting cells able to trigger the adaptive immune response to specific antigens. When non-self-antigens are captured, DCs switch from an "immature" to a "mature" state to fulfill their function. Among the several surface proteins involved in DCs maturation, the role of aquaporins (AQPs) is still poorly understood. Here we investigated the expression profile of Aqps in murine bone marrow derived dendritic cells (BMDCs). Among the Aqps analyzed, Aqp9 was the most expressed by DCs. Its expression level was significantly upregulated 6 h following LPS exposure. Chemical inhibition of Aqp9 led to a decreased inflammatory cytokines secretion. BMDCs from AQP9-KO mice release lower amount of inflammatory cytokines and chemokines and increased release of IL-10. Despite the reduced release of inflammatory cytokines, Aqp9-KO mice were not protected from DSS induced colitis. All together, our data indicate that AQP9 blockade can be an efficient strategy to reduce DCs inflammatory response but it is not sufficient to protect from acute inflammatory insults such as DSS induced colitis