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The use of ultrasound (US) in combination with a responsive chemical agent (sonosensitizer) can selectively trigger the agent’s anticancer activity in a process called sonodynamic therapy (SDT). SDT shares some properties with photodynamic therapy (PDT), which has been clinically approved, but sets itself apart because of its use of US rather than light to achieve better tissue penetration. SDT provides anticancer effects mainly via the sonosensitizer-mediated generation of reactive oxygen species (ROS), although the precise nature of the underpinning mechanism is still under debate. This work investigates the SDT anticancer activity of hypericin (Hyp) in vitro in two- (2D) and three-dimensional (3D) HT-29 colon cancer models, and uses PDT as a yardstick due to its well-known Hyp phototoxicity. The cancer cell uptake and cellular localization of Hyp were investigated first to determine the proper noncytotoxic concentration and incubation time of Hyp for SDT. Furthermore, ROS production, cell proliferation, and cell death were evaluated after Hyp was exposed to US. Since cancer relapse and transporter-mediated multidrug resistance (MDR) are important causes of cancer treatment failure, the US-mediated ability of Hyp to elicit immunogenic cell death (ICD) and overcome MDR was also investigated. SDT showed strong ROS-mediated anticancer activity 48 h after treatment in both the HT-29 models. Specific damage-associated molecular patterns that are consistent with ICD, such as calreticulin (CRT) exposure and high-mobility group box 1 protein (HMGB1) release, were observed after SDT with Hyp. Moreover, the expression of the ABC transporter, P-glycoprotein (P-gp), in HT-29/MDR cells was not able to hinder cancer cell responsiveness to SDT with Hyp. This work reveals, for the first time, the US responsiveness of Hyp with significant anticancer activity being displayed, making it a full-fledged sonosensitizer for the SDT of cancer.

Background: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. Objectives: To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. Methods: This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Results: Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: p = 0.525; 90-days: p = 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: p = 0.002; 90-days: p < 0.001). Delta-PCT was associated with a lower 28-days (p = 0.007; OR = 0.12, 95%CI 0.02–0.46) and 90-days mortality (p = 0.001; OR = 0.17, 95%CI 0.06–0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: p = 0.047; 90-days: p = 0.049). Severe vitamin D deficiency was associated with a higher 28-days (p = 0.058; OR = 3.95, 95%CI 1.04–19.43) and 90-days mortality (p = 0.054; OR = 2.94, 95%CI 1.00–9.23). Conclusions: Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.

The use of ultrasound (US) in combination with a responsive chemical agent (sonosensitizer) can selectively trigger the agent's anticancer activity in a process called sonodynamic therapy (SDT). SDT shares some properties with photodynamic therapy (PDT), which has been clinically approved, but sets itself apart because of its use of US rather than light to achieve better tissue penetration. SDT provides anticancer effects mainly via the sonosensitizer-mediated generation of reactive oxygen species (ROS), although the precise nature of the underpinning mechanism is still under debate. This work investigates the SDT anticancer activity of hypericin (Hyp) in vitro in two- (2D) and three-dimensional (3D) HT-29 colon cancer models, and uses PDT as a yardstick due to its well-known Hyp phototoxicity. The cancer cell uptake and cellular localization of Hyp were investigated first to determine the proper noncytotoxic concentration and incubation time of Hyp for SDT. Furthermore, ROS production, cell proliferation, and cell death were evaluated after Hyp was exposed to US. Since cancer relapse and transporter-mediated multidrug resistance (MDR) are important causes of cancer treatment failure, the US-mediated ability of Hyp to elicit immunogenic cell death (ICD) and overcome MDR was also investigated. SDT showed strong ROS-mediated anticancer activity 48 h after treatment in both the HT-29 models. Specific damage-associated molecular patterns that are consistent with ICD, such as calreticulin (CRT) exposure and high-mobility group box 1 protein (HMGB1) release, were observed after SDT with Hyp. Moreover, the expression of the ABC transporter, P-glycoprotein (P-gp), in HT-29/MDR cells was not able to hinder cancer cell responsiveness to SDT with Hyp. This work reveals, for the first time, the US responsiveness of Hyp with significant anticancer activity being displayed, making it a full-fledged sonosensitizer for the SDT of cancer. [ABSTRACT FROM AUTHOR]

The development of solid‐state electrochromics (EC) represents an emerging challenge towards effective integration with other optoelectronic units, such as the EC‐organic light‐emitting diode devices (EC‐OLEDs). By a simultaneous or independent control of optical contrast (EC function) and OLED emission upon electrical activation, these fascinating systems are capable of adaptively modulating solar radiation and display lighting. Here, we report a flexible ECOLED on a single‐plastic substrate demonstrating how the rational design of a highly efficient and durable solid‐state EC cell enables an increase of overall performances and the integration with OLED on larger area and flexible substrate. The resulting device shows high transparency and optical contrast (ΔT650nm = 60%), with lower operating voltages (0.5–3 V), faster coloring/bleaching switching times (5–10 s), and enhanced stability (1000 switching cycles) if compared to similar systems. The OLED unit reveals a luminance of 1000 cd m−2 (at 10 mA cm−2) and a current efficiency of about 10 cd A−1, making it suitable for both display and lighting applications. These results can represent a novelty in the field of next‐generation smart windows and transparent displays, including all technologies based on see‐through OLED displays, electronic devices for augmented reality, lighting panels and smart glasses. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Sepsis is a life-threatening disease resulting from the interaction between pathogen and host response; its dysregulation causes organ dysfunction, high morbidity, and mortality. Despite the increase of septic patients admitted to Internal Medicine wards, data about clinical predictors of mortality in this setting are still lacking. The aim of this study was to evaluate the role of MEDS score and vitamin D as predictors of mortality (28-day and 90-day) in septic patients admitted to the Internal Medicine department. PATIENTS AND METHODS: Prospectively collected clinical data, lab tests including vitamin D, and clinical scores (SIRS, MEDS, SCS, REMS, SOFA, qSOFA) were retrospectively analyzed. Eightyeight microbiologically identified septic patients (median age 75 years old, IQR 65-82 years old; range 37-94 years old) were evaluated. RESULTS: Twenty-three patients (26.1%) died at 28 days, 33 (37.5%) died at 90 days. The logistic regression showed a positive effect of MEDS score (p=0.006; OR 1.24, 95% CI 1.08-1.49), and a negative effect of low vitamin D levels (p=0.008, OR 0.83, 95% CI 0.72-0.94) on mortality. Moreover, the cut-off of 7 points for MEDS score and of 7 ng/ml for vitamin D levels significantly predicted poor prognosis at 28 and 90 days. CONCLUSIONS: MEDS score and vitamin D levels represent independent predictors of mortality in a cohort of Internal Medicine septic patients. Further studies on larger samples are needed to confirm our results and to clarify the pathophysiological mechanisms at the basis of vitamin D deficiency as a predictor of mortality in septic patients. [ABSTRACT FROM AUTHOR]

The integration of energy-saving electrochromic systems with novel functions and features in a single smart multifunctional device promises to achieve remarkable technological advancements for a wide range of consumer products showing more versatility, responsivity to different external inputs, and ability to operate in interactive modes. Here, we report a novel architecture in which a solid-state electrochromic cell and a solid-state organic light emitting diode are fully integrated in a single, highly transparent, solid-state electrochromic OLED device. This multifunctional device is capable of tuning its optical properties such as transmittance (chromic transition) and of producing light by electroluminescence, simultaneously or independently. The rational design of the solid-state electrochromic cell and the highly transparent OLED enables the construction of the integrated device in a monolithic unit. In such a structure the photonic architecture of the OLED device not only guarantees high transmittance, but, operating synergically with the electrochromic component, it outperforms the optical properties and electrochromic responses by the interference phenomenon, achieveing an optical contrast of 57% (ΔTbleaching/colouring @ 650 nm), and a coloration efficiency of 169 cm2 C−1, with very low energy consumption (80 mW cm−2). The OLED component exhibits luminance above the minimum values required for display and lighting applications, which are 300 cd m−2 and above 800 cd m−2, respectively. This result represents a further step towards the development of next-generation multifunctional EC devices such as full solid-state photoelectrochromic devices, and, importantly, this can open the way for new electrochromic “smart” window systems such as retail display windows or display EC glasses for augmented reality. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Chronic alcohol abuse represents a risk factor for oral diseases, in particular, oral cancer. Periodontal disease has been showed to be involved in the pathophysiology of cardiovascular and metabolic diseases, such as atherosclerosis and liver steatosis. The role of chronic alcohol consumption on periodontitis is still controversial. The aim of the study was to evaluate the effect of chronic alcohol abuse on oral health. PATIENTS AND METHODS: Twenty-three alcohol use disorders (AUD) patients and twenty-three healthy social drinkers underwent an oral examination by trained oral clinicians in order to evaluate oral and dental health. A questionnaire assessing oral hygiene was administered together with the evaluation of DMFT (decayed, missing, filled teeth), SLI (Silness-Loë plaque index) and CPI (community periodontal index of treatment needs) scores. RESULTS: Alcoholic patients showed significantly lower oral hygiene scores compared to controls. Alcoholic patients showed significantly poorer scores at DMFT, SLI and CPI tests. Moreover, among alcoholics, smokers showed a significantly poorer oral health than non-smokers. CONCLUSIONS: Chronic alcohol abuse increases the risk of dental and periodontal diseases. Smoking represents a significant co-factor. The practice of basic oral hygiene and the access to professional dental care should be encouraged among AUD patients in order to reduce oral diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] We synthesized POEA-MWNTs nanocomposites by in situ chemical oxidative polymerization. [•] Conducting polymer chains simply wrapped up around MWNTs with no strong interaction. [•] Polymer chains growing process is enhanced by very low concentration of MWNTs. [•] Possibility of tuning the chemicophysical properties in relation of the CNTs content. [Copyright &y& Elsevier]

This paper considers the problem of scheduling nonpreemptive jobs on identical parallel processors to minimize workload balancing criteria. While workload balancing is an important practical criterion given the need of production systems to efficiently use all of their resources, there is no established measure of performance in the scheduling literature that characterizes total workload balance. In this paper, the normalized standard deviation, the normalized mean deviation, and the normalized mean difference are proposed as criteria that measure the balance of the workloads among the machines associated to a schedule. A local search algorithm, which performs multiple exchanges of jobs among machines, is presented. The results of a wide computational experimentation demonstrate that the proposed algorithm performs well for all the proposed measures. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work is the assessment of the possibility to produce geopolymeric materials for the specific use in the field of consolidation of stone materials or as restoration mortars, through mechanochemical activation of two solid precursors, quartz and kaolin. These starting materials were modified by grinding at different times and then the degree of reactivity of the obtained products was verified by studying the changes induced by the mechanical treatment on the crystalline structure and by determining the specific surface. Moreover the solubility and kind of alkaline solutions classically used for the production of geopolymeric materials (NaOH and KOH) was investigated together with other aqueous solutions at variable pH. The mechano-chemical activation process can achieve the result to reduce the use of alkaline solutions as activators of the starting raw materials in the production of consolidating solution for monument stone materials and to utilise natural materials in the production of restoration mortars compatible with the substrates to be restored. [Copyright &y& Elsevier]

Cell--cell adhesion plays a fundamental role in cell polarity and organogenesis. It also contributes to the formation and establishment of physical barriers against microbial infections. However, a large number of pathogens, from viruses to bacteria and parasites, have developed countless strategies to specifically target cell adhesion molecules in order to adhere to and invade epithelial cells, disrupt epithelial integrity, and access deeper tissues for dissemination. The study of all these processes has contributed to the characterization of molecular machineries at the junctions of eukaryotic cells that have been better understood by using pathogens as probes. [ABSTRACT FROM AUTHOR]

A 3 1/2-year-old female presented with Turner's syndrome and Nonne-Milroy-Meige disease. Ocular findings included strabismus and bilateral chemosis which was unchanging and persisted throughout the four years the patient was followed up. Histopathological findings included diffuse lymphangiectasia and dense connective tissue surrounding the dilated lymph channels. Although the association between congenital lymphoedema and Turner's syndrome is common, the lymphoedema usually disappears by the first year of life. The persistence of the lymphoedema beyond this age is rare, as is the presence of the persistent chemosis. This report represents the first histopathological documentation of congenital lymphangiectasis in association with Turner's syndrome. [ABSTRACT FROM PUBLISHER]

Electrochromic devices (ECDs) represent one of the most promising energy saving and solar control technology for the market of energy‐efficient building and optoelectronic devices. A continuous and intense effort is currently devoted to the development of effective solid‐state ECDs and their integration in multifunctional systems, such as photoelectrochromics. Here, the fabrication of simplified all‐solid‐state WO3 based ECDs on single‐substrate is reported, demonstrating how the rational design of highly interconnected WO3 columnar nanostructures with Nafion polymer matrix remarkably decreases the charge transport barrier at the hybrid electrolyte/electrochromic interface (EEI), thus determining an impressive improvement of overall device performances. The soft polymer substrate of the electrolyte plays a key role on the formation of WO3 pillar‐like structures and on the increase of interfacial contact area by affecting the vacuum‐deposition WO3 growth. Apart from providing higher transmittance in bleached state, the resulting device, entirely manufactured at room temperature by bottom‐up process, exhibits lower activation voltages (0.5–3 V) and faster switching kinetics (5–10 s) compared with monolithic ECDs based on both bulk and mesoporous WO3 films. Furthermore, the enhanced EEI enables the scale‐up on large area and flexible substrate ensuring simultaneously a wide optical contrast (ΔT = 70%), and high coloration efficiency. [ABSTRACT FROM AUTHOR]

Purpose To describe an approach to diversity, equity, and inclusion (DEI) strategy development at a school of pharmacy aimed at stakeholder investment and infrastructure that can address systemic challenges in various healthcare settings. Summary The UNC Eshelman School of Pharmacy utilized an organizational approach focused on infrastructure to produce a diverse and inclusive school community. The Office of Organizational Diversity and Inclusion (ODI) established vision and mission statements to represent the school's commitment and conducted a comprehensive environmental scan to compose a shared vision. Students, faculty, staff, and alumni participated in a series of retreats, symposiums, and focus groups to identify opportunities to cultivate a diverse and inclusive school community. A working group comprised of key leaders in the school developed and launched a 3-year DEI Strategic Plan along with initiatives and metrics for year 1. The plan's 3 priorities were (1) to recruit and retain diverse talent, (2) to prepare culturally intelligent professionals, and (3) to build an inclusive community. The ODI collaborated with internal and external stakeholders, which included students, faculty, staff, postdocs, alumni, and partners from health systems, industry, and other institutions and organizations, to initiate, implement, and monitor progress through an organizational approach to establish accountability and greater commitment. Conclusion An organizational approach to DEI strategy through stakeholder engagement and infrastructure increased commitment and shared ownership among members of the school community. Applications in an organizational approach can be adapted to multiple healthcare settings to contribute to the cultural transformation necessary to develop a diverse and inclusive healthcare workforce. [ABSTRACT FROM AUTHOR]

Background Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Methods Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Results Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. Conclusions The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. [ABSTRACT FROM AUTHOR]