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PurposeCritical infrastructure (CI) plays an essential role in reading, reacting and responding while dealing with natural disasters. This study address food supply chain resilience by proposing an FSC resilience model that explains the food product and transport flow via production, processing, distribution and retailing in circumstances of (CI) collapses post a natural disaster.Design/methodology/approachA combination of qualitative methods was conducted to obtain a comprehensive overview of the food and beverage sector in Puerto Rico. The full dataset comprised of seven focus groups for a total of 52 participants and 12 in-depth interviews.FindingsFSC resilience is seen in this study through the managerial actions taken by members of the Chain: innovating, transforming, adapting, and flexibilising business models and operations.Originality/valueThis study is the first to address FSC resilience from the perspective of net food importer economy in the context of natural disasters and prolonged Critical infrastructure (CI) breakdown, and the first one in proposing an FSC resilience model that explains the food product and transport flow via production, processing, distribution and retailing in circumstances of CI collapses post a natural disaster.

This study demonstrates that switching from calcineurin inhibitors to sirolimus had an antitumoral effect in kidney-transplant recipients with cutaneous squamous-cell carcinomas and may have implications concerning immunosuppressive treatment of such patients. Skin cancers affect more than half of organ-transplant recipients during their long-term course. 1 Several studies have shown that after a first cutaneous squamous-cell carcinoma, multiple subsequent skin cancers develop in 60 to 80% of kidney-transplant recipients within 3 years. 2 , 3 Transplant recipients share common risk factors with the nonimmunosuppressed population, 4 but the specific tumor burden of such patients is linked to the immunosuppressive medications used. 5 , 6 A decrease in cutaneous carcinogenesis after the reduction of immunosuppression has been reported. 7 Consequently, changes in immunosuppression are frequently made in patients with skin cancer, although there is currently no consensus on the level . . .

Enzyme-catalyzed production of biodiesel is the object of extensive research due to the global shortage of fossil fuels and increased environmental concerns. Herein we report the preparation and main characteristics of a novel biocatalyst consisting of Cross-Linked Enzyme Aggregates (CLEAs) of Candida antarctica lipase B (CALB) which are covalently bound to magnetic nanoparticles, and tackle its use for the synthesis of biodiesel from non-edible vegetable and waste frying oils. For this purpose, insolubilized CALB was covalently cross-linked to magnetic nanoparticles of magnetite which the surface was functionalized with -NH2 groups. The resulting biocatalyst combines the relevant catalytic properties of CLEAs (as great stability and feasibility for their reutilization) and the magnetic character, and thus the final product (mCLEAs) are superparamagnetic particles of a robust catalyst which is more stable than the free enzyme, easily recoverable from the reaction medium and reusable for new catalytic cycles. We have studied the main properties of this biocatalyst and we have assessed its utility to catalyze transesterification reactions to obtain biodiesel from non-edible vegetable oils including unrefined soybean, jatropha and cameline, as well as waste frying oil. Using 1% mCLEAs (w/w of oil) conversions near 80% were routinely obtained at 30°C after 24 h of reaction, this value rising to 92% after 72 h. Moreover, the magnetic biocatalyst can be easily recovered from the reaction mixture and reused for at least ten consecutive cycles of 24 h without apparent loss of activity. The obtained results suggest that mCLEAs prepared from CALB can become a powerful biocatalyst for application at industrial scale with better performance than those currently available.

In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. Sirolimus (rapamycin) suppresses mTOR signaling and was studied in this 18-month open-label, randomized, controlled trial involving adults with ADPKD and early chronic kidney disease. Sirolimus at a daily target dose of 2 mg did not halt polycystic kidney growth. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary kidney disease and the cause of end-stage renal disease in 7 to 10% of all patients undergoing dialysis. 1 – 3 The disease is characterized by the growth of numerous kidney cysts, which leads to progressive destruction of the adjacent renal parenchyma and massive enlargement of the kidneys. 4 Renal function is often preserved until the age of 40 years because functioning nephrons undergo compensatory hypertrophy. 5 Subsequently, the glomerular filtration rate (GFR) decreases, and end-stage renal disease ensues in many patients by the fifth decade. As yet, no treatment is available to . . .

ObjectiveTo assess the contribution of regional grey matter (GM) atrophy and functional disconnection in determining the level of cognitive decline in patients with Alzheimer's disease (AD) at different clinical stages.MethodsTen patients with amnesic mild cognitive impairment (a-MCI), 11 patients with probable AD and 10 healthy controls were recruited. T1 volumes were obtained from each subject and postprocessed according to an optimised voxel based morphometry protocol. Resting state functional MRI data were also collected from the same individuals and analysed to produce connectivity maps after identification of the default mode network (DMN) by independent component analysis.ResultsCompared with healthy controls, both AD and a-MCI patients showed a similar regional pattern of brain disconnection between the posterior cingulate cortex (PCC) and the medial prefrontal cortex and the rest of the brain. Conversely, the distribution of GM atrophy was significantly more restricted in a-MCI than in AD patients. Interestingly, the PCC showed reduced connectivity in a-MCI patients in the absence of GM atrophy, which was, in contrast, detectable at the stage of fully developed AD.ConclusionsThis study indicates that disconnection precedes GM atrophy in the PCC, which is a critical area of the DMN, and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflects a long term effect of brain disconnection. In this context, our study indicates that GM atrophy in PCC accompanies the conversion from MCI to AD.

•Two thirds of hospitals systematically implement some nutritional screening tool.•Most used nutritional screening tools are NRS 2002 (Nutrition Risk Screening) and NUTRIC Score (Nutrition risk in critically ill).•Nutritional evaluations most used are anthropometry and SGA (Subjective Global Assessment).•Prevalence of malnutrition at admission shows expected values, yet lower than that described in other reports from Latin America.•A low percentage of hospitals count on multidisciplinary nutritional support.•Low use of oral nutritional supplements. We describe the status of medical nutrition therapy in adult patients in several hospitals in Latin America in 2023. with the aim of deepening understanding of its implementation and thus, in turn, contributing to the advancement of future guidelines. This is a descriptive, multicenter, cross-sectional study. An electronic questionnaire was applied, containing screening, nutritional therapy, multidisciplinary nutritional support, and monitoring indicators. Descriptive statistics were used in data processing. A total of 132 hospitals from 14 Latin American countries participated; 68.2% were state-owned with a median of 23,804 patients. In 66% of hospitals (n = 87) nutritional screening is systematically implemented; NRS-2002 (n = 66; 75.9%) applied mostly by dietitians. Median malnutrition at admission was 33% (IQR = 30.8). Median indication for diet therapy was 54.4% (IQR = 44.3); oral supplementation 13.6% (IQR = 18), and enteral and parenteral nutritional support 14.6% (IQR = 10.2). Indication is carried out mostly by dietitians (n = 78; 59.1%). 29.5% (n = 39) of hospitals count on multidisciplinary nutritional support. 75% (n = 99) use industrialized formulas, mostly in closed systems (n = 53; 40.2%). For parenteral nutrition, individually compounded and preprepared solutions are used (n = 71; 53.8%) generally administered by central catheters. Most frequently cited monitoring indicators were hemodynamic instability, metabolic complications, abdominal distension, and gastric residue. There are still low implementation percentages of nutritional screening, formation of nutritional therapy teams, and use of oral supplements. Malnutrition upon admission is within the expected range.

Deranged calcium-phosphate metabolism contributes to the burden of morbidity and mortality in dialysis patients. This study aimed to assess the association of the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality. We measured soluble Klotho and FGF23 levels at enrolment and two weeks later in 239 prevalent hemodialysis patients. The primary hypothesis was that low Klotho and high FGF23 are associated with increased mortality. The association between Klotho and atrial fibrillation (AF) at baseline was explored as secondary outcome. AF was defined as presence of paroxysmal, persistent or permanent AF. During a median follow-up of 924 days, 59 (25%) patients died from any cause. Lower Klotho levels were not associated with mortality in a multivariable adjusted analysis when examined either on a continuous scale (HR 1.25 per SD increase, 95% CI 0.84-1.86) or in tertiles, with tertile 1 as the reference category (HR for tertile two 0.65, 95% CI 0.26-1.64; HR for tertile three 2.18, 95% CI 0.91-2.23). Higher Klotho levels were associated with the absence of AF in a muItivariable logistic regression analysis (OR 0.66 per SD increase, 95% CI 0.41-1.00). Higher FGF23 levels were associated with mortality risk in a multivariable adjusted analysis when examined either on a continuous scale (HR 1.45 per SD increase, 95% CI 1.05-1.99) or in tertiles, with the tertile 1 as the reference category (HR for tertile two 1.63, 95% CI 0.64-4.14; HR for tertile three 3.91, 95% CI 1.28-12.20). FGF23 but not Klotho levels are associated with mortality in hemodialysis patients. Klotho may be protective against AF.

DNA methylation and the machinery involved in epigenetic regulation are key elements in the maintenance of cellular homeostasis. Epigenetic mechanisms are involved in embryonic development and the establishment of tissue-specific expression, X-chromosome inactivation and imprinting patterns, and maintenance of chromosome stability. The balance between all the enzymes and factors involved in DNA methylation and its interpretation by different groups of nuclear factors is crucial for normal cell behaviour. In cancer and other diseases, misregulation of epigenetic marks is a common feature, also including DNA methylation and histone post-translational modifications. In this scenario, it is worth mentioning a family of proteins characterized by the presence of a methyl-CpG-binding domain (MBDs) that are involved in interpreting the information encoded by DNA methylation and the recruitment of the enzymes responsible for establishing a silenced state of the chromatin. The generation of novel aberrantly hypermethylated regions during cancer development and progression makes MBD proteins interesting targets for their biological and clinical implications.

Background Patients undergoing invasive mechanical ventilation often require pharmacologic sedation to facilitate tolerance of this life-sustaining intervention, but sedatives currently used in routine care have substantial limitations. Isoflurane is an inhaled volatile anesthetic with pharmacologic properties potentially suitable to sedation of ventilator-dependent critically ill patients, but need for specialized drug administration equipment has limited its use historically to general anesthesia in the operating theatre. This trial will evaluate isoflurane, administered using a novel drug delivery system, for sedation of ventilator-dependent adult intensive care unit (ICU) patients in the United States (US). Methods The Inhaled Sedation versus Propofol in Respiratory Failure in the ICU (INSPiRE-ICU2) is a phase 3, multicenter, randomized, controlled, assessor-blinded non-inferiority trial that will evaluate efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S, compared to intravenous propofol, for sedation of mechanically ventilated adult ICU patients. At 16 US hospitals, 235 enrolled patients requiring continuous sedation during invasive mechanical ventilation will be randomized in 1.5:1 ratio to inhaled isoflurane or intravenous propofol for sedation. Treatment duration is expected to be at least 12 h and may last up to 48 (± 6) h or until no longer needing continuous sedation, whichever occurs first. The primary endpoint is the percentage of time sedation depth is maintained within the targeted range (Richmond Agitation Sedation Scale − 1 to − 4), in the absence of rescue sedation, during the treatment period. Secondary superiority outcomes include opioid exposure, wake-up time, cognitive recovery after end-of-treatment, and preservation of spontaneous breathing effort. Discussion The INSPiRE-ICU2 trial will help determine the potential role of isoflurane for sedation of ventilator-dependent adult patients in the ICU. Key trial design features, including adoption of the estimand framework and blinded assessments of sedation depth, pain, and cognitive recovery, will ensure a rigorous evaluation of isoflurane for ICU sedation. Trial registration ClinicalTrials.gov, NCT05327296. First registered on April 5, 2022.

In autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is regarded as an important biomarker of disease progression and different methods are available to assess kidney volume. The purpose of this study was to identify the most efficient kidney volume computation method to be used in clinical studies evaluating the effectiveness of treatments on ADPKD progression. We measured single kidney volume (SKV) on two series of MR and CT images from clinical studies on ADPKD (experimental dataset) by two independent operators (expert and beginner), twice, using all of the available methods: polyline manual tracing (reference method), free-hand manual tracing, semi-automatic tracing, Stereology, Mid-slice and Ellipsoid method. Additionally, the expert operator also measured the kidney length. We compared different methods for reproducibility, accuracy, precision, and time required. In addition, we performed a validation study to evaluate the sensitivity of these methods to detect the between-treatment group difference in TKV change over one year, using MR images from a previous clinical study. Reproducibility was higher on CT than MR for all methods, being highest for manual and semiautomatic contouring methods (planimetry). On MR, planimetry showed highest accuracy and precision, while on CT accuracy and precision of both planimetry and Stereology methods were comparable. Mid-slice and Ellipsoid method, as well as kidney length were fast but provided only a rough estimate of kidney volume. The results of the validation study indicated that planimetry and Stereology allow using an importantly lower number of patients to detect changes in kidney volume induced by drug treatment as compared to other methods. Planimetry should be preferred over fast and simplified methods for accurately monitoring ADPKD progression and assessing drug treatment effects. Expert operators, especially on MR images, are required for performing reliable estimation of kidney volume. The use of efficient TKV quantification methods considerably reduces the number of patients to enrol in clinical investigations, making them more feasible and significant.