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Background: Tractography allows the in vivo study of subcortical white matter, and it is a potential tool for providing predictive indices on post-operative outcomes. We aim at establishing whether there is a relation between cognitive outcome and the status of the inferior fronto-occipital fasciculus’s (IFOF’s) microstructure. Methods: The longitudinal neuropsychological data of thirty young (median age: 35 years) patients operated on for DLGG in the left temporo-insular cortex along with pre-surgery tractography data were processed. Results: A degraded integrity of the left (vs. right) IFOF (lower fractional anisotropy and length, p < 0.001; higher mean and axial diffusivity, p < 0.01) was found, with lower microstructural variables in the infiltration (vs. dislocation) group. Significant decreases immediately post-surgery vs. pre-surgery mainly occurred in lexico-semantics (p < 0.001), with significant improvements at follow-up in all the tests (p < 0.01 to p < 0.001), despite values in the range of 44% to 47.82% of patients with below cut-off scores regarding naming verbs and making visual lexical decisions. The status of left and right IFOFs is predictive of a decrease in immediate post-surgery performance for several tests (p < 0.05); similarly, it is predictive of better recovery in the follow-up performance for naming nouns, naming verbs, making phonological fluency lexical decisions, and the token test (p < −0.05). For the ROC analysis, a significant result was obtained for the verb-naming test, with a cut-off of 79%. Conclusions: This study supports the role of the predictive value of pre-operative tractography for assessing the immediate post-operative result and at follow-up the risk of developing a cognitive deficit.

Background: Ethnic differences in coronary atherosclerosis remain to be fully elucidated. We aimed to assess quantitative plaque characteristics from coronary CT Angiography (CCTA) in relation to ethnicity and cardiovascular risk factors in a multi-ethnic asymptomatic US population. Methods: This cross-sectional study retrospectively evaluated 388 asymptomatic patients selected from a prospective CCTA registry. A total of 194 patients from ethnic minority groups (Asian, African American, and Hispanic) were matched by age, sex, and cardiovascular risk factors to 194 White patients. Quantitative plaque volumes—including total plaque, non-calcified plaque, low-attenuation non-calcified plaque (

Trace elements (TEs) in anaerobic digestion (AD) are known to be essential for optimal biogas production, but inhibitive in excessive concentrations. However, the mechanisms of inhibition are not fully understood. The effects of the addition essential TEs (Co, Cu and Ni) and a non-essential TE (Cd) on the microbial community structure of AD were studied in lab-scale reactors, using total TE concentrations that ranged from 0 to 100 μM. Reactor performance was assessed by monitoring biogas production. The labile fraction of TEs (the most bioaccessible species) was determined by diffusive gradients in thin-films technique. Prokaryotic community composition was characterized through high throughput sequencing (HTS) targeting archaea and bacteria and qPCR to evaluate changes in methanogens and metal resistance genes. Only a minor fraction of added TEs was labile and it decreased over time, with Ni being the most labile. Although only a minor fraction of spiked concentration was labile, all TEs inhibited biogas production at the highest spiking concentration (100 μM), with higher inhibition observed for Cd and Ni. HTS and qPCR revealed changes, particularly in archaea, with reduced relative abundance at higher TE concentrations. Shifts in prokaryotic communities suggest alterations in AD metabolic pathways. High inhibition of biogas was linked to reduced diversity, dominance of the bacterial genus Klebsiella and changes in the ratio acetoclastic / hydrogenotrophic methanogens. This study addresses a research gap in understanding how TEs inhibit AD, and provides a strategy to improve TE dosing by monitoring the labile fraction of TEs to avoid overdosing.

Cetaceans are key sentinel species of marine ecosystems and ocean health, being a strategic taxonomic group that evaluates the well-being of aquatic habitats and detects harmful environmental trends. Respiratory diseases are amongst the main causes of death in these animals, so identifying the microbiome community in their exhaled breath condensates (EBC), i.e. blow, has been proposed as a key biomarker for assessing respiratory health. Yet, to characterise microbiomes related to these animals’ respiratory tract and use them as a proxy for health status, it is necessary to develop baseline data on the microorganisms associated with cetaceans. Here, the short-finned pilot whale (SFPW, Globicephala macrorhynchus) was used as a case study to validate the most suitable primer set to explore the prokaryotic diversity of the cetaceans’ respiratory tract. DNA extracted from blow samples (n = 12) of animals off Madeira Island was sequenced to amplify both V3-V4 and V4-V5 hypervariable regions of the 16S rRNA gene, using the same sequencing platform (Illumina MiSeq). Independently of the primer set used, all blows shared Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria phyla in their composition. V3-V4 resulted in a higher diversity of taxa with relative abundance above 1%, whereas the V4-V5 primers captured a higher number of microbial Amplicon Sequence Variants, detecting the rare microbial biosphere with pathogen potential. Additionally, it captured the core microbiome more efficiently. Thus, this study provides a detailed characterisation of SFPW respiratory-associated microbial communities, strengthening the idea of sociality influencing microbiome composition in the respiratory tract. Moreover, it supports the use of blow as a relevant biomarker for the physiological state of the airways in free-ranging cetaceans.

Systemic hypertension, a significant global health issue and a leading risk factor for cardiovascular mortality affects half of the adult population, with increasing prevalence notably in low- and middle-income countries. Despite advancements in diagnosis and treatment, only one in four individuals with hypertension achieve satisfactory control over their condition. Medication adherence, critical for effective hypertension management, is complex and multifaceted. Non-adherence, encompassing late or non-initiation, sub-optimal implementation, and early discontinuation of treatment, is prevalent worldwide, with reported rates of anti-hypertensive medication non-adherence ranging from 30% to 40%. Adherence is influenced by various factors including drug regimen complexity, patient education, and socioeconomic status. Poor adherence is linked to increased cardiovascular risks and is compounded by clinical inertia among physicians. Addressing barriers to adherence and implementing evidence-based interventions can significantly reduce the global burden of hypertension and its associated complications. This review highlighted the critical need for improved adherence strategies to enhance hypertension management. It focused on novel tools such as mobile health interventions and regimen-simplification through single-pill combinations, which can improve treatment persistence and blood pressure control.

Microbial communities are crucial for important ecosystem functions in the open ocean, such as primary production and nutrient cycling. However, few studies have addressed the distribution of microplankton communities in the remote oligotrophic region of the Pacific Ocean. Moreover, the biogeochemical and physical drivers of microbial community structure are not fully understood in these areas. This research aims to investigate the patterns of prokaryotic and protists communities’ distribution in the North Pacific Subtropical Front (NPSF). The NPSF is a vast oligotrophic region with layered surface water and strong ocean currents. Despite its considerable size, its community distribution and function are poorly studied. We used a 16S and 18S rRNA gene sequencing approach to identify and characterize the water column microbial communities at two depths, the surface (3–5 m) and the deep chlorophyll maximum (DCM, 108–130 m). We aimed to elucidate the horizontal distribution patterns of these communities and to dissect the factors intricately shaping their distribution in the NPSF. Results showed that the community structure of both prokaryotes and protists was significantly influenced by depth, temperature, and longitude. Regarding alpha diversity, both communities presented a higher diversity at the surface. The prokaryotes also demonstrated to have a higher diversity in samples placed further east. The prokaryotes were dominated by Proteobacteria and Cyanobacteria, and the eukaryotic communities were dominated by Syndiniales. Combining biological and hydrographic data analysis showed the influence of vertical currents near the frontal jet in shaping the vertical distribution of both prokaryotic and protist communities. Even though most studies do not consider anomalies that emerge at each depth, these occurrences are capable of having a strong impact and influence on community structure. This study marks a significant advance in unraveling the intricate community structure and distribution dynamics of marine microbial communities within the North Pacific Ocean.

Background Sex‐related differences in Takotsubo syndrome have been described, but no information is available in patients who develop cardiogenic shock. Methods and Results Of 412 patients with Takotsubo syndrome with cardiogenic shock, 71 (17.2%) were men. Male patients were older (71.1±12.2 versus 65.3±17.1 years, P

ABSTRACTBackgroundThrombotic microangiopathy (TMA) is a pathological syndrome characterized by a combination of three key features: microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage, primarily affecting the kidneys. There are several drugs known to have a definite or probable causal association with TMA, and carfilzomib, a second‐generation irreversible proteasome inhibitor (PI), approved for the treatment of multiple myeloma (MM), is one of them. In the medical literature, there have been a growing number of reports describing this serious adverse event occurring in MM patients. The precise mechanisms underlying the development of PI‐induced TMA are not yet fully understood. Significant improvements in both renal and hematological aspects have been documented following the administration of eculizumab.Recent FindingsIn this report, we present two cases of MM patients who developed TMA while undergoing carfilzomib therapy. These cases were successfully treated at the Haematology Unit, Careggi Hospital in Florence. In our cases as well, the introduction of eculizumab resulted in rapid enhancements in renal function and platelet count, ultimately leading to the discontinuation of hemodialysis after 4 and 2 weeks, respectively.Discussion and ConclusionWe assessed 91 patients who received carfilzomib‐based therapies at our Haematology Department, during which we identified two cases of DITMA (2.2% incidence). Additionally, we conducted a literature review and discovered a total of 75 documented cases of carfilzomib‐induced TMA. Our experience aligns with the cases reported in literature: this adverse event can manifest at any point during treatment, regardless of the specific drug combinations used alongside carfilzomib. The initial and most crucial step in its management involves discontinuing carfilzomib therapy; therefore, recognizing TMA in a timely manner is of utmost importance. Eculizumab could play a role in improving and expediting the resolution of this potentially fatal adverse event, but further studies are needed. In a MM patient receiving carfilzomib, presenting with anemia, thrombocytopenia, and impaired renal function, a carfilzomib‐induced TMA should be suspected in order to discontinue the causative agent.

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.

Background/Objectives: Ventriculoperitoneal shunting is a validated procedure for the treatment of idiopathic normal-pressure hydrocephalus. To select shunt-responsive patients, infusion and tap tests can be used. Only gait is evaluated after the procedure to establish a potential improvement. In this study, we present our Hydro-Real-Time Neuropsychological Testing protocol to assess the feasibility of performing an ultra-fast assessment of patients during the infusion and tap test. Methods: We tested 57 patients during the infusion and tap test to obtain real-time feedback on their cognitive status. Data were obtained immediately before the infusion phase (T0), when the pressure plateau was reached (T1), and immediately after cerebrospinal fluid subtraction (T2). Based on cerebrospinal fluid dynamics, 63.15% of the patients presented a resistance to outflow > 12 mmHg/mL/min, while 88% had a positive tap test response. Results: Compared to T0, cerebrospinal fluid removal significantly improved performance on tasks exploring executive functions (counting backward, p < 0.001; verbal fluency, p < 0.001). Patients were significantly faster at counting backward at T2 vs. T1 (p < 0.05) and at T2 vs. T0 (p < 0.001) and were significantly faster at counting forward at T2 vs. T1 (p < 0.005), suggesting an improvement in speed at T2. There was a significantly smaller index at T1 vs. T0 (p = 0.005) and at T2 vs. T0 (p < 0.001), suggesting a more marked improvement in patients’ executive abilities at T2 and a smaller improvement at T1. Regarding verbal fluency, patients were worse at T1 vs. T0 (p < 0.001) and at T2 vs. T0 (p < 0.001). Conclusions: Patients’ performance can be monitored during the infusion and tap test as significant changes in executive functions are observable. In future, this protocol might help improve patients’ selection for surgery.

Malaria, an infectious disease with a tremendous impact on human health is caused by Plasmodium parasites, and transmitted by Anopheles mosquitoes. New approaches to control the disease involve transmission blocking strategies aiming to target the parasite in the mosquito. Here, we investigated the putative inhibitory activity of essential oils and their components on the early mosquito stages of the parasite. We employed an in vitro assay of gametocyte-to-ookinete development of the rodent model parasite Plasmodium berghei combined with high content screening. 60 essential oils with known composition were tested. The results revealed that fifteen EOs had inhibitory activity. Furthermore, a machine learning approach was used to identify the putative inhibitory components. Five of the most important chemical components indicated by the machine learning-based models were actually confirmed by the experimental approach. This combined approach was used for the first time to identify the potential transmission blocking activity of essential oils and single components at the zygote and ookinete stages.

Given the increasing pressure on water bodies, it is imperative to explore sustainable methodologies for wastewater treatment and reuse. The simultaneous presence of multiples contaminants in complex wastewater, such as the liquid effluents from biogas plants, can compromise biological treatment effectiveness for reclaiming water. Vertical subsurface flow constructed wetlands were established as low-cost decentralized wastewater treatment technologies to treat the liquid fraction of digestate from municipal organic waste with metals, antibiotics, and antibiotic resistance genes, to allow its reuse in irrigation. Twelve lab-scale planted constructed wetlands were assembled with gravel, light expanded clay aggregate and sand, testing four different treating conditions (liquid digestate spiked with oxytetracycline, sulfadiazine, or ofloxacin, at 100 μg/ L, or without dosing) during 3 months. Physicochemical parameters (pH, chemical oxygen demand (COD), nutrients, metals, and antibiotics), the microbial communities dynamics (through 16S high-throughput sequencing) and antibiotic resistance genes removal (qPCR) were monitored in influents and effluents. Systems removed 85.8%–96.9% of organic matter (as COD), over 98.1% of ammonium and phosphate ions, and 69.3%–99.4% of nitrate and nitrite ions, with no significant differences between the presence or absence of antibiotics. Removal of Fe, Mn, Zn, Cu, Pb and Cr exceeded 82% in all treatment cycles. The treatment also removed oxytetracycline, sulfadiazine and ofloxacin over 99%, and decreased intl1, tetA, tetW, sul1 and qnrS gene copies. Nonetheless, after 3 months of ofloxacin dosing, qnrS gene started being detected. Removal processes relied on high HRT (14 days) and various mechanisms including sorption, biodegradation, and precipitation. Microbial community diversity in liquid digestate changed significantly after treatment in constructed wetlands with a decrease in the initial Firmicutes dominance, but with no clear effect of antibiotics on the microbial community structure. Removals above 85% and 94% were observed for Streptococcus and Clostridium, respectively. Results suggest that vertical subsurface flow constructed wetlands were a suitable technology for treating the liquid digestate to reuse it in irrigation agricultural systems, contributing to the circular bioeconomy concept. However, a more profound understanding of effective wastewater treatment strategies is needed to avoid antibiotic resistance genes dissemination.

The paper reports the results of a research targeted to develop a Decision Support System (DSS) for planning and operation of urban deliveries carried out with electric vans. The research was included within the 2019-21 Research Program for the Electric System, coordinated by the Italian Ministry for the Ecological Transition, and has been performed by ENEA, the Italian Agency for Energy, New Technologies and Sustainable Development, and “La Sapienza” University of Rome. The new DSS is based on meta-heuristics algorithms capable to manage a generic set of goods to be delivered by means of a generic fleet of electric vans, with the objective of minimizing the overall cost of the daily operation. The algorithm considers all the physical constraints, including vehicles batteries capacity. It is assumed that fast recharges can be performed during the delivery tours. For the real-time operation, a monitoring system of the vehicle fleet, road network and recharge stations is assumed, based on IoT technologies, in order to detect possible unexpected events and manage them in the best way, according to the available resources time by time. The paper describes the DSS general architecture, the optimization algorithms and the recovery procedures and shows results for two testbeds.

Background. Incidentally discovered low-grade gliomas (iLGGs) are very rare and little is still known about their associated functional imaging activation patterns, white-matter status, and plasticity potential. Recent studies shed light on several clinical factors responsible for the good clinical status observed in these patients versus those with their symptomatic counterpart (sLGGs), including small volume. Comparisons were typically carried out by comparing iLGGs with the wider and more heterogeneous sLGG group. In this study, we investigated whether iLGGs affect the brain differently from comparably small sLGGs. Method. Starting from a sample of 13 patients with iLGG, in the current comparative cross-sectional study, we identified a group of patients with sLGGs, primarily matched by lesion volume. We looked for potential differences between the two groups in language-related functional and structural parameters (the fMRI network associated with naming and white-matter fascicles). Results. The t-test did not show significant differences in the fMRI network, but these emerged when performing masking. No significant differences were observed at the white-matter level. Conclusions. Given that small volumes characterized both groups and that demographic variables were comparable, too, we hypothesized that differences between the two groups could be attributed to alternative lesion-related parameters. We discussed these findings from clinical and neurosurgical perspectives.

Background Cardiogenic shock (CS) is a significant complication of Takotsubo syndrome (TTS), contributing to heightened mortality and morbidity. Despite this, the Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks validation in patients with TTS and CS. This study aimed to characterize a patient cohort with TTS using the SCAI staging system and assess its utility in cases of TTS complicated by CS. Methods and Results From a TTS national registry, 1591 consecutive patients were initially enrolled and stratified into 5 SCAI stages (A through E). Primary outcome was all‐cause in‐hospital mortality; secondary end points were TTS‐related in‐hospital complications and 1‐year all‐cause mortality. After exclusions, the final cohort comprised 1163 patients, mean age 71.0±11.8 years, and 87% were female. Patients were categorized across SCAI shock stages as follows: A 72.1%, B 12.2%, C 11.2%, D 2.7%, and E 1.8%. Significant variations in baseline demographics, comorbidities, clinical presentations, and in‐hospital courses were observed across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage showed a significant association with increased in‐hospital mortality (adjusted odds ratio: 1.77–29.31) compared with SCAI shock stage A. Higher SCAI shock stages were also associated with increased 1‐year mortality. Conclusions In a large multicenter patient cohort with TTS, the functional SCAI shock stage classification effectively stratified mortality risk, revealing a continuum of escalating shock severity with higher stages correlating with increased in‐hospital mortality. This study highlights the applicability and prognostic value of the SCAI staging system in TTS‐related CS.