Search

Abstract Background Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers. Methods The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. Interviews sought to understand attitudes/beliefs and barriers/facilitators to chemoprevention. Results Interviews with 25 providers (18 physicians and 7 advanced practice providers) were included. Providers were predominantly female (84%), white (72%), and non-Hispanic (88%). Nearly all providers (96%) had prescribed chemoprevention for eligible patients. Three themes emerged in qualitative analysis. The first theme describes providers’ confidence in chemoprevention and the utility of decision support tools. The second theme elucidates barriers to chemoprevention, including time constraints, risk communication and perceptions of patients’ fear of side effects and anxiety. The third theme is the need for early implementation of decision support tools. Conclusions This qualitative study suggests that providers were interested in the early inclusion of decision aids (DA) in their chemoprevention discussion workflow. The DAs may help overcome certain barriers which were elucidated in these interviews, including patient level concerns about side effects, clinic time constraints and difficulty communicating risk. A multi-faceted intervention with a DA as one active component may be needed. Trial registration This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT04496739.

This article presents the ENglish Reading Online (ENRO) project that offers data on English reading and listening comprehension from 7,338 university-level advanced learners and native speakers of English representing 19 countries. The database also includes estimates of reading rate and seven component skills of English, including vocabulary, spelling, and grammar, as well as rich demographic and language background data. We first demonstrate high reliability for ENRO tests and their convergent validity with existing meta-analyses. We then provide a bird's-eye view of first (L1) and second (L2) language comparisons and examine the relative role of various predictors of reading and listening comprehension and reading speed. Across analyses, we found substantially more overlap than differences between L1 and L2 speakers, suggesting that English reading proficiency is best considered across a continuum of skill, ability, and experiences spanning L1 and L2 speakers alike. We end by providing pointers for how researchers can mine ENRO data for future studies.

Abstract Background In cardiovascular disease, high blood pressure is associated with oxidative stress, promoting endothelial dysfunction, vascular remodeling, and inflammation. Clinical trials are discordant that the most effective treatment in the management of hypertension seems to be the administration of anti-hypertensive drugs with antioxidant properties. The study aims to evaluate the effects of the eutomer of thioctic acid on oxidative stress and inflammation in the heart of spontaneously hypertensive rats compared to normotensive Wistar Kyoto rats. Methods To study the oxidative status, the malondialdehyde and 4-hydroxynonenal concentration, protein oxidation were measured in the heart. Morphological analysis were performed. Immunohistochemistry and Western blot were done for alpha-smooth muscle actin and transforming growth factor beta to assess fibrosis; cytokines and nuclear factor kappaB to assess inflammatory processes. Results Spontaneously hypertensive rats were characterized by hypertension with increased malondialdehyde levels in the heart. OxyBlot in the heart of spontaneously hypertensive rats showed an increase in proteins’ oxidative status. Cardiomyocyte hypertrophy and fibrosis in the ventricles were associated with an increased expression of alpha-smooth muscle actin and pro-inflammatory cytokines, reduced by the eutomer of thioctic acid supplementation. Conclusions Based on this evidence, eutomer of thioctic acid could represent an appropriate antioxidant molecule to reduce oxidative stress and prevent inflammatory processes on the cardiomyocytes and cardiac vascular endothelium.

Purpose – After the identification of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Wuhan, China, a pandemic was widely spread worldwide. In Italy, about 240,000 people were infected because of this virus including 34,721 deaths until the end of June 2020. To control this new pandemic, epidemiologists recommend the enforcement of serious mitigation measures like country lockdown, contact tracing or testing, social distancing and self-isolation. Design/methodology/approach – This paper presents the most popular epidemic model of susceptible (S), exposed (E), infected (I) and recovered (R) collectively called SEIR to understand the virus spreading among the Italian population. Findings – Developed SEIR model explains the infection growth across Italy and presents epidemic rates after and before country lockdown. The results demonstrated that follow-up of strict measures such that country lockdown along with high testing is making Italy practically a pandemic-free country. Originality/value – These models largely help to estimate and understand how an infectious agent spreads in a particular country and how individual factors can affect the dynamics. Further studies like classical SEIR modeling can improve the quality of data and implementation of this modeling could represent a novelty of epidemic models.

Cerebrovascular pressure reactivity plays a key role in maintaining constant cerebral blood flow. Unfortunately, this mechanism is often impaired in acute traumatic neural injury states, exposing the already injured brain to further pressure-passive insults. While there has been much work on the association between impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) and worse long-term outcomes, there is yet to be a comprehensive review on the association between cerebrovascular pressure reactivity and intracranial pressure (ICP) extremes. Therefore, we conducted a systematic review of the literature for all studies presenting a quantifiable statistical association between a continuous measure of cerebrovascular pressure reactivity and ICP in a human TBI cohort. The methodology described in the Cochrane Handbook for Systematic Reviews was used. BIOSIS, Cochrane Library, EMBASE, Global Health, MEDLINE, and SCOPUS were all searched from their inceptions to March of 2023 for relevant articles. Full-length original works with a sample size of ?10 patients with moderate/severe TBI were included in this review. Data were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 16 articles were included in this review. Studies varied in population characteristics and statistical tests used. Five studies looked at transcranial Doppler-based indices and 13 looked at ICP-based indices. All but two studies were able to present a statistically significant association between cerebrovascular pressure reactivity and ICP. Based on the findings of this review, impaired reactivity seems to be associated with elevated ICP and reduced ICP waveform complexity. This relationship may allow for the calculation of patient-specific ICP thresholds, past which cerebrovascular reactivity becomes persistently deranged. However, further work is required to better understand this relationship and improve algorithmic derivation of such individualized ICP thresholds.

Research into second language (L2) reading is an exponentially growing field. Yet, it still has a relatively short supply of comparable, ecologically valid data from readers representing a variety of first languages (L1). This article addresses this need by presenting a new data resource called "MECO L2" (Multilingual Eye Movements Corpus), a rich behavioral eye-tracking record of text reading in English as an L2 among 543 university student speakers of 12 different L1s. MECO L2 includes a test battery of component skills of reading and allows for a comparison of the participants' reading performance in their L1 and L2. This data resource enables innovative large-scale cross-sample analyses of predictors of L2 reading fluency and comprehension. We first introduce the design and structure of the MECO L2 resource, along with reliability estimates and basic descriptive analyses. Then, we illustrate the utility of MECO L2 by quantifying contributions of four sources to variability in L2 reading proficiency proposed in prior literature: reading fluency and comprehension in L1, proficiency in L2 component skills of reading, extralinguistic factors, and the L1 of the readers. Major findings included (a) a fundamental contrast between the determinants of L2 reading fluency versus comprehension accuracy, and (b) high within-participant consistency in the real-time strategy of reading in L1 and L2. We conclude by reviewing the implications of these findings to theories of L2 acquisition and outline further directions in which the new data resource may support L2 reading research.

Background: Non-prescription antibiotic use is defined as taking antibiotics without medical guidance, which includes using leftover antibiotics, obtaining antibiotics from friends or relatives, or purchasing antibiotics without a prescription. This study aimed to (1) determine the symptoms prompting individuals to use non-prescription antibiotics, identify their sources of acquisition, and document the types of antibiotics utilized, (2) identify any associated side effects, and (3) gain insights into antibiotic storage practices, including whether antibiotics were used beyond their expiration date. Methods: A cross-sectional quantitative survey was conducted from January 2020-June 2021 in waiting rooms of six safety-net primary care clinics and two private emergency departments in Houston, Texas. Participants were read survey questions in English or Spanish by a bilingual research coordinator, and their responses to five questions about antibiotic use were recorded. Descriptive analysis was performed. Results: Among the 564 patients surveyed, the median age was 51 (range 19-92). The majority identified as female (72%), Hispanic/Latinx (47%), Black/African American (33%), held a college education (44%), and received public health insurance, such as Medicaid or County Financial Assistance (56%). Of all patients surveyed, 44% (246) reported taking an antibiotic without a prescription and answered questions about associated symptoms. Of all symptoms/illnesses associated with non-prescription use, the most common were sore throat (18%), dental symptoms (16%), and cold/flu (13%). The most common sources for non-prescribed antibiotics were leftover antibiotics (50%), from friends or relatives (31%), and purchased abroad (13%), although 3% had purchased non-prescription antibiotics from a local store or market (Figure 1). The most common antibiotics used were amoxicillin (38%) and penicillin (7%). The reported side effects were stomach pain/upset (24%), nausea and vomiting (19%), allergic reaction (e.g., rash) (14%), and diarrhea (14%). Among 246 participants reporting antibiotic use, 63% reported that the antibiotic they took had been previously prescribed for the same symptom/illness, and 93% had acquired antibiotics in a container, of which 90% reported that the container had an expiration date. Conclusions: Our survey reveals that 63% of individuals who use non-prescription antibiotics were motivated by having received prescribed antibiotics for similar symptoms previously. Leftover antibiotics were the source for half of all non-prescription use. These observations suggest that outpatient antibiotic stewardship campaigns have a window of opportunity at the time of the initial prescription of antibiotics, to focus on providing the shortest course possible, and to deliver antibiotic safe use information at that time. Acknowledgments: Financial Support AHRQ R01HS026901

Introduction: The organizational readiness for change assessment survey (ORCA) is a tool to assess a site’s readiness for implementation and identify barriers to change. As the “Kicking CAUTI” antibiotic stewardship intervention rolled out on a national scale, we administered ORCA surveys to participating sites to capture baseline actionable information about differences among sites, to inform implementation. Methods: ORCA surveys were distributed by email to prescribing providers, nurses, pharmacists, infection preventionists, and quality managers at 40 participating VA Hospitals. VA hospital sites who submitted three or more surveys and their complexity level (measured as Level 1 (highest)-3) were included in the analysis. The highest complexity level facilities are those with the largest patient volume/risk, teaching and research, along with the largest number of physician specialists and contain at least five ICUs. Mean Likert scores were calculated for each of the 7 ORCA subscales on a scale of 1-5 (5 highest), and the mean of the 7 subscales was the overall ORCA score for a site. Non-parametric testing was performed comparing overall ORCA and each subscale based on complexity. Results: Among the participating sites, 30/40 (75%) completed at least three surveys, with a total of 202 surveys included for analysis, with 82% of surveys coming from higher complexity centers (Level 1). The highest ranked ORCA domain was the evidence subscale (measures perceived strength of evidence), mean 4.2, (SD 0.7). The lowest ranked ORCA domain across sites was resources (available to facilitate implementation), mean 3.3 (SD 0.9). Higher complexity centers had a significantly higher overall ORCA score than lower complexity centers (Level 1 or 2 vs. Level 3, p= 0.02). This difference was driven by the subscales evidence (p < 0 .01), leadership (p =0.05), measurement (p= 0.06), and resources (p=0.07) all being higher in the higher complexity facilities (Figure 1). Two of the categories (leadership and measurement) pertain to an organization’s leaders ability to create an environment for change to occur as well as promoting team building. Conclusions: The lowest scoring ORCA domain across all sites was the respondents’ perception of resources (staff, training) available for achieving change. Perceived resources were also lower in lower complexity sites, implying that medical centers of lower complexity may have higher barriers when implementing an antimicrobial stewardship intervention. This finding highlights the benefit of a national stewardship campaign that provides support to lower complexity medical centers that may not otherwise receive targeted training and support for their efforts.

Abstract Background Optimal cerebral perfusion pressure (CPPopt) has emerged as a promising personalized medicine approach to the management of moderate-to-severe traumatic brain injury (TBI). Though literature demonstrating its association with poor outcomes exists, there is yet to be work done on its association with outcome transition due to a lack of serial outcome data analysis. In this study we investigate the association between various metrics of CPPopt and failure to improve in outcome over time. Methods CPPopt was derived using three different cerebrovascular reactivity indices; the pressure reactivity index (PRx), the pulse amplitude index (PAx), and the RAC index. For each index, % times spent with cerebral perfusion pressure (CPP) above and below its CPPopt and upper and lower limits of reactivity were calculated. Patients were dichotomized based on improvement in Glasgow Outcome Scale-Extended (GOSE) scores into Improved vs. Not Improved between 1 and 3 months, 3 and 6 months, and 1- and 6-month post-TBI. Logistic regression analyses were then conducted, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Results This study included a total of 103 patients from the Winnipeg Acute TBI Database. Through Mann–Whitney U testing and logistic regression analysis, it was found that % time spent with CPP below CPPopt was associated with failure to improve in outcome, while % time spent with CPP above CPPopt was generally associated with improvement in outcome. Conclusions Our study supports the existing narrative that time spent with CPP below CPPopt results in poorer outcomes. However, it also suggests that time spent above CPPopt may not be associated with worse outcomes and is possibly even associated with improvement in outcome.

The use of inulin in food is highly appreciated by consumers because of its prebiotic effect. In this study, the effects of increasing additions (5, 10 and 20%) of inulin as a substitute for wheat flour in bread production were investigated with regard to the physical, technological and rheological properties of the flour blends. Inulin reduced the water-binding capacity from 1.4 g/100 g with 0 flour to 0.80 g/100 g with the 20% inulin addition, while there were no statistical differences in the oil-binding capacity. The addition of inulin also influenced the yeast rates, especially in the samples with 5 and 10% addition. On the farinograph, inulin caused a reduction in water absorption (40.75 g/100 g with 20% inulin), an increase in dough development time (18.35 min with 10% inulin) and dough stability (13.10 min with 10% inulin). The mixograph showed a longer kneading time for the sample with 20% inulin (8.70 min) than for the control (4.61 min). In addition, there was an increase in dough firmness and tightness due to the addition of inulin (W: 203 × 10−4 J; P/L: 4.55 for the 20% inulin sample) compared with the control. The physical and technological properties of the loaves were evaluated at time 0 and after 4 days (T4). The addition of inulin reduced the volume of the bread while increasing the weight, albeit with a weight loss at T4 (compared to T0) of 4.8% for the 20% inulin and 14.7% for the control. The addition of inulin caused a darkening of the crust of the enriched bread, proportional to the increase in inulin content. In addition, the inulin content ranged from 0.82 g/100 g in the control to 14.42 g/100 g in the 20% inulin bread, while the predicted glycemic index ranged from 94.52 in the control to 89.39 in the 20% inulin bread. The available data suggest that the formulation with 5% inulin provides the highest performance.

The agri-food processing industry predominantly relies on fossil fuels, contributing significantly to greenhouse gas emissions and extensive water use. Climate change requires a conversion of food processing technologies towards sustainability. Our research focuses on testing and validating pulsed electric field (PEF) technology as a mild processing method for stabilizing freshly squeezed, not from concentrate, blood orange juice. Experiments were carried out on a continuous pilot plant endowed with a patented treatment chamber that ensures a constant flow of product without “hot spots” for a homogeneous treatment. Once the operative conditions of the process in terms of energy density were optimized, PEF-treated blood orange juice was tested in order to evaluate the effects on physico-chemical parameters (total soluble solids, total acidity, pH, CIE L*, a*, b*, C*, h color indices, cloud, bioactive compounds (ascorbic acid, total anthocyanins, total and individual flavanones), antioxidant activity (ORAC units, total phenolic content), microbial communities (aerobic mesophilic viable count, yeasts and molds, acid-tolerant microorganisms), residual enzymatic pectinmethylesterase activity, and sensory attributes (flavor, off-flavor, off-odor, color, intensity of odor, acidity, sweetness, bitter, freshness, cooked flavor). Then, in order to simulate the commercial refrigerated distribution of PEF-treated blood orange juice and define its refrigerated shelf-life, the PEF-treated freshly squeezed, not from concentrate, blood orange juice was subjected to physico-chemical, antioxidant, microbiological, and sensory evaluations over twenty days of refrigerated storage at 4 ± 1 °C. The PEF treatment effectively ensured excellent microbial inactivation and enhanced the nutritional and health characteristics of the juice, thereby extending its shelf-life. This study demonstrates the significant potential of the PEF treatment to produce blood orange juice suitable for a new retail segment—freshly squeezed juices with superior health quality, fresh-like characteristics, and extended refrigerated shelf-life.

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of IFI, as the diagnosis was made using 28S rDNA/internal transcribed spacer PCR.

For the original publication [...]

This study investigates sustainable extraction protocols for the recovery of bioactive compounds from by-products of various pomegranate (Punica granatum L.) cultivars, including Acco, Hicaz, Jolly Red, Parfianka, Valenciana, and Wonderful, generated during the industrial processing of the fruits. Advanced extraction technologies, including ultrasounds, microwaves, and hydrodynamic cavitation, have been compared to conventional extraction procedures and utilized to enhance extraction efficiency while also minimizing environmental impact. Water-based extraction methods have been utilized to promote the development of sustainable and eco-friendly processes. The comparison between conventional extractions and ultrasound-assisted extractions (UAEs) and microwave-assisted extractions (MAEs) demonstrated notable improvements in extraction yields, particularly for ellagitannins (punicalins, punicalagins, and ellagic acid) and total polyphenols, with increases ranging from about 45 to 200%. However, the increases directly comparing UAEs to MAEs ranged from about 4 to 6%. This indicates that while both UAEs and MAEs offer notable improvements over conventional extractions, the differences in extraction efficiency between the two advanced methods were relatively modest. These advancements were observed across various pomegranate cultivars, highlighting the versatility and effectiveness of these methods. Notably, hydrodynamic cavitation-based extractions (HC) emerged as particularly promising, consistently yielding the highest levels of bioactive compounds (ellagitannins and total polyphenols), especially when operated at higher frequencies. Compared to conventional extractions, HC exhibited substantial increases in extraction yields for Wonderful pomegranate by-products, surpassing the efficiency of both UAEs and MAEs (approximately 45 and 57% for UAE and MAE, respectively, versus about 80% for HC). Among these advanced techniques, HC has emerged as particularly promising, yielding the most favorable results and leading to significant improvements in the yield of bioactive compounds. When directly compared to UAEs and MAEs, HC increased extraction yields by over 20%. Furthermore, HC allowed for shorter extraction times. The Wonderful cultivar consistently exhibited the highest levels of ellagitannins and the highest total polyphenol content among all types of extraction procedures used, whether conventional or advanced. This highlights the great potential of the Wonderful cultivar in terms of bioactive compound extraction and underscores its significance in research and applications related to pomegranate processing and utilization. This study suggests that the implementation of these advanced technologies into extraction processes represents a significant advancement in the field, offering a promising avenue for the development of efficient and environmentally friendly extraction methods for obtaining valuable bioactive compounds from pomegranate processing by-products.

Background and Objectives: The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer’s disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer’s disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. Materials and Methods: This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. Discussion: This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. Registration: EudraCT number: 2020-000576-38

In the original publication [...]

To optimally assess oscillatory phenomena within physiological variables, spectral domain transforms are used. A discrete Fourier transform (DFT) is one of the most common methods used to attain this spectral change. In traumatic brain injury (TBI), a DFT is used to derive more complicated methods of physiological assessment, particularly that of cerebrovascular reactivity (CVR). However, a practical application of a DFT will introduce various errors that need to be considered. This study will evaluate the pulse amplitude DFT derivation of intracranial pressure (AMP) to highlight how slight differences in DFT methodologies can impact calculations. Utilizing a high-frequency prospectively maintained data set of TBI patients with recorded arterial and intracranial blood pressure, various cerebral physiological aspects of interest were assessed using the DFT windowing methods of rectangular, Hanning, and Chebyshev. These included AMP, CVR indices (including the pressure reactivity and pulse amplitude index), and the optimal cerebral perfusion pressure (with all methods of CVR). The results of the different DFT-derived windowing methods were compared using the Wilcoxon signed-ranked test and histogram plots between individual patients and over the whole 100-patient cohort. The results for this analysis demonstrate that, overall and for grand average values, there were limited differences between the different DFT windowing techniques. However, there were individual patient outliers to whom the different methods resulted in noticeably different overall values. From this information, for derived indices utilizing a DFT in the assessment of AMP, there are limited differences within the resulting calculations for larger aggregates of data. However, when the amplitude of spectrally resolved response is important and needs to be robust in smaller moments in time, it is recommended to use a window that has amplitude accuracy (such as Chebyshev or flat-top).

Within traumatic brain injury (TBI) care, there is growing interest in pathophysiological markers as surrogates of disease severity, which may be used to improve and individualize care. Of these, assessment of cerebrovascular reactivity (CVR) has been extensively studied given that it is a consistent, independent factor associated with mortality and functional outcome. However, to date, the literature supports little-to-no impact of current guideline-supported therapeutic interventions on continuously measured CVR. Previous work in this area has suffered from a lack of validation studies, given the rarity of time-matched high-frequency cerebral physiology with serially recorded therapeutic interventions; thus, we undertook a validation study. Utilizing the Winnipeg Acute TBI database, we evaluated the association between daily treatment intensity levels, as measured through the therapeutic intensity level (TIL) scoring system, and continuous multi-modal?derived CVR measures. CVR measures included the intracranial pressure (ICP)-derived pressure reactivity index, pulse amplitude index, and RAC index (a correlation between the pulse amplitude of ICP and cerebral perfusion pressure), as well as the cerebral autoregulation measure of near-infrared spectroscopy-based cerebral oximetry index. These measures were also derived over a key threshold for each day and were compared to the daily total TIL measure. In summary, we could not observe any overall relationship between TIL and these CVR measures. This validates previous findings and represents only the second such analysis to date. This helps to confirm that CVR appears to remain independent of current therapeutic interventions and is a potential unique physiological target for critical care. Further work into the high-frequency relationship between critical care and CVR is required.

Abstract Background Although vasopressor and sedative agents are commonly used within the intensive care unit to mediate systemic and cerebral physiology, the full impact such agents have on cerebrovascular reactivity remains unclear. Using a prospectively maintained database of high-resolution critical care and physiology, the time-series relationship between vasopressor/sedative administration, and cerebrovascular reactivity was interrogated. Cerebrovascular reactivity was assessed through intracranial pressure and near infrared spectroscopy measures. Using these derived measures, the relationship between hourly dose of medication and hourly index values could be evaluated. The individual medication dose change and their corresponding physiological response was compared. Given the high number of doses of propofol and norepinephrine, a latent profile analysis was used to identify any underlying demographic or variable relationships. Finally, using time-series methodologies of Granger causality and vector impulse response functions, the relationships between the cerebrovascular reactivity derived variables were compared. Results From this retrospective observational study of 103 TBI patients, the evaluation between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies was completed. The assessment of the physiology pre/post infusion agent change resulted in similar overall values (Wilcoxon signed-ranked p value > 0.05). Time series methodologies demonstrated that the basic physiological relationships were identical before and after an infusion agent was changed (Granger causality demonstrated the same directional impact in over 95% of the moments, with response function being graphically identical). Conclusions This study suggests that overall, there was a limited association between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies including that of cerebrovascular reactivity. Thus, current regimens of administered sedative and vasopressor agents appear to have little to no impact on cerebrovascular reactivity in TBI.

Abstract Introduction The simulation exercise (SimEx) simulates an emergency in which an elaboration or description of the response is applied. The purpose of these exercises is to validate and improve plans, procedures, and systems for responding to all hazards. The purpose of this study was to review disaster preparation exercises conducted by various national, non-government, and academic institutions. Methodology Several databases, including PubMed (Medline), Cumulative Index to Nursing and Allied Health Literature (CINAHL), BioMed Central, and Google Scholar, were used to review the literature. Information was retrieved using Medical Subject Headings (MeSH) and documents were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To assess the quality of the selected articles, the Newcastle-Ottawa Scale (NOS) technique was utilized. Results A total of 29 papers were selected for final review based on PRISMA guidelines and the NOS quality assessment. Studies have shown that many forms of SimEx commonly used in disaster management including tabletop exercises, functional exercises, and full-scale exercises have their benefits and limitations. There is no doubt that SimEx is an excellent tool for improving disaster planning and response. It is still necessary to give SimEx programs a more rigorous evaluation and to standardize the processes more thoroughly. Conclusions Drills and training can be improved for disaster management, which will enable medical professionals to face the challenges of disaster management in the 21st century.

The aim of the paper is to examine the linguistic varieties present in the autobiographical diary of an illiterate Sicilian peasant woman, Carolina Drago, who has chosen to entrust her memoirs to the written page. The diary, composed since 2007, when Carolina Drago was more than 70 years old, contains recipes of gastronomic preparations, prayers, songs as well as the narration of the most significant episodes of her existence seen through the eyes and heart of a mother who writes the diary in order to deliver her memories to her children and grandchildren. The facts described within only partially intertwine the "great history" (e.g. the Spanish epidemic of the twenties, the Second World War) and dwell rather on the family environment, offering a crosssection of peasant and popular life that crosses the twentieth century. From a linguistic point of view, Carolina Drago uses the variety of the repertoire at her disposal: basically, the dialect and popular regional Italian, mixing the linguistic colours of her poor palette with the enthusiasm of those who want to tell and tell themselves. A linguistic analysis will also be presented, aimed at demonstrating how the writings of illiterate people allow us to see that Italian defined as "hidden" by Testa (2014), almost in a karstic way, has continued to evolve alongside the normative codification anticipating innovative trends.