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Assemblies of one-dimensional filaments appear in a wide range of physical systems: from biopolymer bundles, columnar liquid crystals, and superconductor vortex arrays; to familiar macroscopic materials, like ropes, cables, and textiles. Interactions between the constituent filaments in such systems are most sensitive to the distance of closest approach between the central curves which approximate their configuration, subjecting these distinct assemblies to common geometric constraints. In this paper, we consider two distinct notions of constant spacing in multi-filament packings in ${{\mathbb{R}}}^{3}$ : equidistance , where the distance of closest approach is constant along the length of filament pairs; and isometry , where the distances of closest approach between all neighboring filaments are constant and equal. We show that, although any smooth curve in ${{\mathbb{R}}}^{3}$ permits one dimensional families of collinear equidistant curves belonging to a ruled surface, there are only two families of tangent fields with mutually equidistant integral curves in ${{\mathbb{R}}}^{3}$ . The relative shapes and configurations of curves in these families are highly constrained: they must be either (isometric) developable domains, which can bend, but not twist; or (non-isometric) constant-pitch helical bundles, which can twist, but not bend. Thus, filament textures that are simultaneously bent and twisted, such as twisted toroids of condensed DNA plasmids or wire ropes, are doubly frustrated: twist frustrates constant neighbor spacing in the cross-section, while non-equidistance requires additional longitudinal variations of spacing along the filaments. To illustrate the consequences of the failure of equidistance, we compare spacing in three ‘almost equidistant’ ansatzes for twisted toroidal bundles and use our formulation of equidistance to construct upper bounds on the growth of longitudinal variations of spacing with bundle thickness.

Human enterovirus 71 (EV71) is a significant cause of morbidity and mortality from Hand, Foot and Mouth Disease (HFMD) and neurological complications, particularly in young children in the Asia-Pacific region. There are no vaccines or antiviral therapies currently available for prevention or treatment of HFMD caused by EV71. Therefore, the development of therapeutic and preventive strategies against HFMD is of growing importance. We report the immunogenic and safety profile of inactivated, purified EV71 preparations formulated with aluminum hydroxide adjuvant in preclinical studies in mice and rabbits. In mice, the candidate vaccine formulations elicited high neutralizing antibody responses. A toxicology study of the vaccine formulations planned for human use performed in rabbits showed no vaccine-related pathological changes and all animals remained healthy. Based on these preclinical studies, Phase 1 clinical testing of the EV71 inactivated vaccine was initiated.

Non-polio enteroviruses, including enterovirus 71 (EV71), have caused severe and fatal cases of hand, foot and mouth disease (HFMD) in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN) receptor deficient) and AG129 (α/β, γ IFN receptor deficient) mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p.) into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m.) in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P

Enterovirus 71 (EV71)-associated hand, foot and mouth disease has emerged as a serious public health problem in South East Asia over the last decade. To better understand the prevalence of EV71 infection, we determined EV71 seroprevalence and seroincidence amongst healthy infants and children in Ho Chi Minh City, Viet Nam. In a cohort of 200 newborns, 55% of cord blood samples contained EV71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. The EV71 neutralizing antibody seroconversion rate was 5.6% in the first year and 14% in the second year of life. In children 5-15 yrs of age, seroprevalence of EV71 neutralizing antibodies was 84% and in cord blood it was 55%. Taken together, these data suggest EV71 force of infection is high and highlights the need for more research into its epidemiology and pathogenesis in high disease burden countries.

Origami structures are characterized by a network of folds and vertices joining unbendable plates. For applications to mechanical design and self-folding structures, it is essential to understand the interplay between the set of folds in the unfolded origami and the possible 3D folded configurations. When deforming a structure that has been folded, one can often linearize the geometric constraints, but the degeneracy of the unfolded state makes a linear approach impossible there. We derive a theory for the second-order infinitesimal rigidity of an initially unfolded triangulated origami structure and use it to study the set of nearly unfolded configurations of origami with four boundary vertices. We find that locally, this set consists of a number of distinct “branches” which intersect at the unfolded state, and that the number of these branches is exponential in the number of vertices. We find numerical and analytical evidence that suggests that the branches are characterized by choosing each internal vertex to either “pop up” or “pop down.” The large number of pathways along which one can fold an initially unfolded origami structure strongly indicates that a generic structure is likely to become trapped in a “misfolded” state. Thus, new techniques for creating self-folding origami are likely necessary; controlling the popping state of the vertices may be one possibility.

Background: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach., Methods: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks., Results: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not., Conclusions: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Red blood cells (RBCs) undergo a progressive morphological transformation from smooth biconcave discocytes into rounder echinocytes with spicules on their surface during cold storage. The echinocytic morphology impacts RBCs' ability to flow through narrow sections of the circulation and therefore transfusion of RBC units with a high echinocytic content are thought to have a reduced efficiency. We use an optical tweezers-based technique where we directly trap and measure linear stiffness of RBCs under stress without the use of attached spherical probe particles or microfluidic flow to induce shear. We study RBC deformability with over 50 days of storage performing multiple stretches in blood plasma (serum with cold agglutinins removed to eliminate clotting). In particular, we find that discocytes and echinocytes do not show significant changes in linear stiffness in the small strain limit ( ∼ 20 % change in length) up to day 30 of the storage period, but do find differences between repeated stretches. By day 50 the linear stiffness of discocytes had increased to approximately that measured for echinocytes throughout the entire period of measurements. These changes in stiffness corresponded to recorded morphological changes in the discocytes as they underwent storage lesion. We believe our holographic trapping and direct measurement technique has applications to directly control and quantify forces that stretch other types of cells without the use of attached probes., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Purpose: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA)., Methods: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction., Results: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p  = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p  = 0.0003; RAD-T2: AUC = 0.79, p  = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p  = 0.0001; COMB-T2: AUC = 0.95, p  = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10 th percentile of signal intensity, while tumor flatness was present in COMB-T2., Conclusion: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.

Purpose: To compare safety, technical and clinical outcomes of double vein embolization (DVE) via a trans-jugular approach with liver venous deprivation (LVD) via a trans-hepatic approach., Materials and Methods: A single-center retrospective analysis was conducted on patients undergoing simultaneous portal and hepatic veins embolization in view of a major hepatectomy (June 2019-November 2022). Hepatic vein embolization was performed either by transjugular plug (DVE) or by transhepatic plug followed by glue injection (LVD). Inclusion criteria were availability of pre-procedural CT scan, and availability of CT scans acquired 10 days and 25 days post-procedure. Comparative data included complication rate, fluoroscopy time, dose area product (DAP), Future Liver Remnant volume and function increase (FLR-V and FLR-F increase, respectively) and clinical outcomes., Results: Thirty-six patients (n = 14 DVE; n = 22 LVD) were included. No baseline significant differences were observed among the two groups. One grade-3 complication (2.8%) was observed in the LVD group; one case of technical failure (2.8%) was observed in the DVE group. Fluoroscopy time and DAP were similar between DVE and LVD (29 ± 17.7 vs. 25 ± 8.2 min, p = 0.97; 105.1 ± 63.5 vs. 143.4 ± 79.5 Gy·cm 2 , p = 0.15). No differences arose at either time-point in FLR-V increase (46.7 ± 23.1% vs. 48.2 ± 28.2%, 52.9 ± 30.9% vs. 53.2 ± 29%, respectively, p = 0.9). FLR-F increase also did not differ significantly (62.8 ± 55.2 vs. 67.4 ± 57.5, p = 0.9). No differences in drop-out rate from surgery were observed. (28.6% vs. 27.3%, p = 0.93). One case of grade-B post-hepatectomy liver failure (2.8%) was observed in the LVD group., Conclusion: LVD via transhepatic approach and DVE via transjugular approach seem equally safe and effective. Level of Evidence Level 3, Retrospective Cohort Study., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose : Among liver hypertrophy technics, liver venous deprivation (LVD) has been recently introduced as an effective procedure to combine simultaneous portal inflow and hepatic outflow abrogation, raising growing clinical interest. The aim of this study is to investigate the role of LVD for preoperative optimization of future liver remnant (FLR) in perihilar cholangiocarcinoma (PHC), especially when compared with portal vein embolization (PVE). Methods : Between January 2013 and July 2022, all patients diagnosed with PHC and scheduled for preoperative optimization of FTR, through radiological hypertrophy techniques, prior to liver resection, were included. FTR volumetric assessment was evaluated at two distinct timepoints to track the progression of both early (T 1 , 10 days post-procedural) and late (T 2 , 21 days post-procedural) efficacy indicators. Post-procedural outcomes, including functional and volumetric analyses, were compared between the LVD and the PVE cohorts. Results : A total of 12 patients underwent LVD while 19 underwent PVE. No significant differences in either post-procedural or post-operative complications were found. Post-procedural FLR function, calculated with (99m) Tc-Mebrofenin hepatobiliary scintigraphy, and kinetic growth rate, at both timepoints, were greater in the LVD cohort (3.12 ± 0.55%/min/m 2 vs. 2.46 ± 0.64%/min/m 2 , p = 0.041; 27.32 ± 16.86%/week (T 1 ) vs. 15.71 ± 9.82%/week (T 1 ) p < 0.001; 17.19 ± 9.88%/week (T 2 ) vs. 9.89 ± 14.62%/week (T 2 ) p = 0.034) when compared with the PVE cohort. Post-procedural FTR volumes were similar for both hypertrophy techniques. Conclusions : LVD is an effective procedure to effectively optimize FLR before liver resection for PHC. The faster growth rate combined with the improved FLR function, when compared to PVE alone, could maximize surgical outcomes by lowering post-hepatectomy liver failure rates.

Purpose: Neutrophil-to-lymphocyte ratio (NLR) recently demonstrated predictive value for hepatocellular carcinoma (HCC) recurrence after thermal ablation. Microwave ablation (MWA) has been shown to induce changes in the immune landscape after HCC treatment. This study aims at identifying predictors of local tumor progression (LTP) and post-treatment NLR kinetics after MWA., Materials and Methods: Data from 108 consecutive patients who underwent percutaneous MWA of 119 HCCs with a 2450 Hz/100 W generator in two institutions from October 2014 to September 2021 were retrospectively reviewed. Forty-five HCCs (42 patients) met inclusion criteria for analysis (technique efficacy, pre- and post-treatment NLR availability, follow-up > 6 months, absence of complications). NLR was analyzed prior to therapy and at 1-month follow-up; difference between the two time points was defined as ΔNLR 1stFU ., Results: After a median follow-up of 25 months, LTP occurred in 18 HCCs (40%) and 18 patients (42.9%). Multivariate competing risk regression comprising ΔNLR 1stFU  > 0, cirrhosis etiology and subcapsular location showed that the only independent predictor of LTP was ΔNLR 1stFU  > 0, on both a per-patient (HR = 2.7, p = 0.049) and per-tumor (HR = 2.8, p = 0.047) analysis. ΔNLR 1stFU  > 0 occurred in 24/42 patients (57.1%). In this subgroup, higher rates of female patients (p = 0.026), higher mean baseline NLR (p < 0.0001) and lower mean energy/size (p = 0.006) were observed. Upon ROC curve analysis, energy/size < 1414 J/mm predicted ΔNLR 1stFU  > 0 with 76% sensitivity and 70% specificity (AUC = 0.74)., Conclusion: NLR increase after ablation was the only independent predictor of LTP, supporting the role of balance between systemic inflammation and immunity in recurrence after MWA. Ablation energy/tumor size predicted NLR increase, reinforcing the concept of immune ablation., Level of Evidence: III., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Epilepsy is a common comorbidity of cerebrovascular disease and an increasing socioeconomic burden., Objective: We aimed to provide an updated comprehensive review on the state of the art about seizures and epilepsy in stroke, cerebral haemorrhage, and leukoaraiosis., Methods: We selected English-written articles on epilepsy, stroke, and small vessel disease up until December 2021. We reported the most recent data about epidemiology, pathophysiology, prognosis, and management for each disease., Results: The main predictors for both ES and PSE are the severity and extent of stroke, the presence of cortical involvement and hemorrhagic transformation, while PSE is also predicted by younger age at stroke onset. Few data exist on physiopathology and seizure semiology, and no randomized controlled trial has been performed to standardize the therapeutic approach to post-stroke epilepsy., Conclusion: Some aspects of ES and PSE have been well explored, particularly epidemiology and risk factors. On the contrary, few data exist on physiopathology, and existing evidence is mainly based on studies on animal models. Little is also known about seizure semiology, which may also be difficult to interpret by non-epileptologists. Moreover, the therapeutic approach needs standardization as regards indications and the choice of specific ASMs. Future research may help to better elucidate these aspects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Angelman syndrome (AS) is a neurogenetic disorder due to deficient expression of the maternal copy of the UBE3A gene, which encodes ubiquitin ligase E3A protein. Severe developmental delay, seizures and other neurological disorders characterize AS., Areas Covered: In this review, we focus on a comprehensive therapeutic approach to the most disabling neurological manifestations of AS: epilepsy, sleep disturbances, behavioral and movement disorders. Articles were identified through PubMed and Google Scholar up to October 2021., Expert Opinion: Evidence for the treatment of neurological manifestations in AS mainly derives from poor quality studies (case reports, small case series, expert opinions). Seizures can be polymorphic and includes atypical absences, myoclonic, generalized tonic-clonic, unilateral clonic, or atonic attacks. Sodium valproate, levetiracetam, and benzodiazepines are the most commonly used anti-seizure medications. Melatonin or mirtazapine seem to improve sleep quality. Antipsychotics, antidepressants, and anxiolytics have been proposed for the treatment of behavioral manifestations, but no evidence-based studies are available. Non-pharmacological approach may also be useful. Mild dystonia is common but usually does not significantly impact patients' motor performances. Well-conducted clinical trials aimed to evaluate treatment of neurological complications of AS are warranted. Gene and molecular precision therapies represent a fascinating area of research in the future.

(1) Background: Breast cancer (BC) is the most prevalent malignancy in women. High cancer-related psychological distress levels have been observed in BC patients, with a potentially relevant impact on disease management, compliance with disease treatments, and everyday life activities and relationships. This work evaluated the effectiveness of three individual cognitive−behavioral therapy psychoeducational sessions versus a self-managed informative guide with individual counseling sessions without specific psychological treatment. (2) Methods: the intervention group received three individual 50-min sessions of psychoeducational training, and the control group received a self-managed informative guide with individual counseling sessions without any kind of psychological treatment. The Hospital Anxiety Depression Scale (HADS), the Distress Thermometer (DT), and the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30 were administered at baseline and two months after study inclusion. (3) Results: A total of 60 participants were included in the study (intervention group: 30, control group: 30). Significant improvements were observed in both groups after two months (p < 0.05), but no statistically significant differences emerged between groups. (4) Conclusions: Psychoeducational interventions and CBT help BC patients manage disease-related fear and distress, allowing them to achieve a good quality of life.

Objective: Sporadic cerebral amyloid angiopathy (CAA) is a degenerative brain small vessel disease of ageing resulting from progressive amyloid deposition in small arteries and arterioles of the cortex and leptomeninges. CAA may be diagnosed by the mean of Boston criteria, particularly with the use of the blood-sensitive T2* MRI sequences (GRE and SWI). Epileptic seizures have rarely been reported in CAA., Patients and Methods: We describe two patients with late-onset unprovoked seizures due to CAA. A short literature review on this topic is presented., Results: In our two patients with late-onset unprovoked seizures as the first manifestation of CAA, only GRE and SWI sequences lead to a correct diagnosis. In literature, only 15 patients with CAA presenting with seizures have been reported. In these subjects, data on seizures semiology and prognosis are scarce., Conclusions: Our report highlights the importance to perform blood-sensitive sequences in all subjects with LOE of otherwise unknown etiology, not to miss a diagnosis of CAA.

Introduction: Cervical dystonia (CD) is one of the most common forms of adult-onset isolated dystonia. Recently, CD has been classified according to the site of onset and spread, in different clinical subgroups, that may represent different clinical entities or pathophysiologic subtypes. In order to support this hypothesis, in this study we have evaluated whether different subgroups of CD, that clinically differ for site of onset and spread, also imply different sensorimotor features. Methods: Clinical and demographic data from 842 patients with CD from the Italian Dystonia Registry were examined. Motor features (head tremor and tremor elsewhere) and sensory features (sensory trick and neck pain) were investigated. We analyzed possible associations between motor and sensory features in CD subgroups [focal neck onset, no spread (FNO-NS); focal neck onset, segmental spread (FNO-SS); focal onset elsewhere with segmental spread to neck (FOE-SS); segmental neck involvement without spread (SNI)]. Results: In FNO-NS, FOE-SS, and SNI subgroups, head tremor was associated with the presence of tremor elsewhere. Sensory trick was associated with pain in patients with FNO-NS and with head tremor in patients with FNO-SS. Conclusion: The frequent association between head tremor and tremor elsewhere may suggest a common pathophysiological mechanism. Two mechanisms may be hypothesized for sensory trick: a gating mechanism attempting to reduce pain and a sensorimotor mechanism attempting to control tremor., (Copyright © 2020 Di Biasio, Marchese, Abbruzzese, Baldi, Esposito, Silvestre, Tescione, Berardelli, Fabbrini, Ferrazzano, Pellicciari, Eleopra, Devigili, Bono, Santangelo, Bertolasi, Altavista, Moschella, Barone, Erro, Albanese, Scaglione, Liguori, Cotelli, Cossu, Ceravolo, Coletti Moja, Zibetti, Pisani, Petracca, Tinazzi, Maderna, Girlanda, Magistrelli, Misceo, Romano, Minafra, Modugno, Aguggia, Cassano, Defazio and Avanzino.)

Background: Acupressure therapy is associated with favourable efficacies on postoperative nausea, pain and sleep disturbance, although the quality of the evidence is generally low. No randomised clinical trial has yet assessed the effect of acupressure on postoperative quality of recovery (QoR)., Objective: The objective was to study acupressure efficacy on patient-reported postoperative recovery., Design: We conducted a single centre, three-group, blind, randomised controlled, pragmatic trial assessing acupressure therapy on the PC6, LI4 and HT7 acupoints., Patients: Postoperative patients expected to stay in hospital at least 2 days after surgery., Interventions: In the acupressure group, pressure was applied for 6 min (2 min per acupoint), three times a day after surgery for a maximum of 2 postoperative days during the hospital stay. In the sham group, extremely light touch was applied to the acupoints. The third group did not receive any touch., Main Outcome Measures: The primary outcome was the change in the QoR, using the QoR-15 questionnaire, between postoperative days 1 and 3. Key secondary outcomes included patients' satisfaction, postoperative nausea and vomiting, pain score and opioid (morphine equivalent) consumption. Assessors for the primary and secondary endpoints were blind to the group allocation., Results: Overall, 163 patients were randomised (acupressure n=55, sham n=53, no intervention n=55). The mean (SD) postoperative change in QoR-15 did not differ statistically (P = 0.27) between the acupressure, sham and no intervention groups: 15.2 (17.8), 14.2 (21.9), 9.2 (21.7), respectively. Patient satisfaction (on a 0 to 10 scale) was statistically different (P = 0.01) among these three groups: 9.1 (1.5), 8.4 (1.6) and 8.2 (2.2), respectively. Changes in pain score and morphine equivalent consumption were not significantly different between the groups., Conclusion: Two days of postoperative acupressure therapy (up to six treatments) did not significantly improve patient QoR, postoperative nausea and vomiting, pain score or opioid consumption. Acupressure, however, was associated with improved patient satisfaction., Trial Registration: ClinicalTrials.gov, identifier: NCT02762435.

Purpose: The purpose of this analysis was to conduct summative usability evaluations, including behavioral and subjective evaluations, for the fentanyl iontophoretic transdermal system (ITS)., Design: Four usability studies were conducted in representative users., Methods: The first three studies were conducted with (1) health care professionals (HCPs; N = 31), (2) patients who received placebo fentanyl ITS (N = 30), and (3) healthy volunteers (N = 30), and focused on the understanding and use of fentanyl ITS. The fourth study included HCPs (N = 31) and healthy volunteers (N = 30), and focused on the effectiveness of formal training regarding the use of fentanyl ITS., Findings: Overall, user groups found the fentanyl ITS easy to use. There were no use errors that could potentially have safety implications. In the three early studies, there were some minor difficulties experienced; however, the introduction of a structured training reduced these difficulties., Conclusions: Patients, nurses, and pharmacists were able to use fentanyl ITS with ease., (Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Acupressure therapy may be potentially beneficial in improving postoperative symptoms like postoperative nausea and vomiting (PONV), pain and sleep disorder and improving postoperative quality of recovery. The primary aim of this study is to investigate the efficacy of acupressure therapy on postoperative patient satisfaction and quality of recovery in hospitalized patients after surgical treatment., Methods/design: This three-group, parallel, superiority, blinded, randomized controlled trial will test the hypothesis that a combination of PC6, LI4 and HT7 acupressure is superior to sham or no intervention for improving postoperative quality of recovery in hospitalized patients. A minimum of 150 patients will be randomly allocated to one of the three experimental groups: control (no visit), light touch (sham acupressure) or active acupressure therapy in a 1:1:1 ratio. Interventions will be performed three times a day for 2 days. Patient satisfaction, quality of recovery, PONV and pain will be measured during the 3 days following randomization. The study protocol was approved by the Stony Brook University Institutional Review Board on 21 March 2016. Written informed consent will be recorded from every consented patient., Discussion: This study has the potential to improve the recovery of hospitalized patients by adding knowledge on the efficacy of acupressure therapy in this setting. A multipoint acupressure protocol will be compared to both a no intervention group and a light touch group, providing insight into different aspects of the placebo effect., Trial Registration: ClinicalTrial.gov, NCT02762435 . Registered on 14 April 2016.

Alzheimer's disease (AD) is a complex, multifactorial progressive neurodegenerative disease. Pathologically, AD is characterized by extracellular deposits of amyloid beta (Aβ) protein and intracellular accumulation of neurofibrillary tangles (NFTs) of tau. The central role of Aβ protein in the AD etiology is well-established, and its increased deposition in AD brain is attributed to its decreased clearance from the brain. It is noteworthy that apolipoprotein E (ApoE), the most significant risk factor for late-onset AD, has been shown to play a vital role in brain Aβ clearance and the ability of ApoE to do this depends mainly upon its lipidation status. Thus, lower ApoE lipidation status leading to decreased Aβ clearance may underlie the increased Aβ deposition observed in AD brain. In addition to the pathophysiological Aβ deposits, AD is also characterized by certain metabolic changes. Among them, decreased cerebral glucose metabolism is one of the distinct characteristics of AD brain and is also observed in patients with Mild Cognitive Impairment (MCI) who subsequently develop AD. Thus, decreased cerebral glucose metabolism is an early event in AD pathology and may precede the neuropathological Aβ deposition associated with AD. In this context, we hypothesize here that the decreased glucose metabolism in pre-AD and early AD stages, may lead to lower ApoE lipidation status, which in turn may lead to decreased clearance and hence, increased deposition of Aβ protein in AD brain., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

As the complexity of analgesic therapies increases, priorities of care must be established to balance aggressive pain management with measures to prevent or minimize adverse events and to ensure high quality and safe care. Opioid analgesia remains the primary pharmacologic intervention for managing pain in hospitalized patients. Unintended advancing sedation and respiratory depression are two of the most serious opioid-related adverse events. Multiple factors, including opioid dosage, route of administration, duration of therapy, patient-specific factors, and desired goals of therapy, can influence the occurrence of these adverse events. Furthermore, there is an urgent need to educate all members of the health care team about the dangers and potential attributes of administration of sedating medications concomitant with opioid analgesia and the importance of initiating rational multimodal analgesic plans to help avoid adverse events. Nurses play an important role in: 1) identifying patients at risk for unintended advancing sedation and respiratory depression from opioid therapy; 2) implementing plans of care to assess and monitor patients; and 3) intervening to prevent the worsening of adverse events. Despite the frequency of opioid-induced sedation, there are no universally accepted guidelines to direct effective and safe assessment and monitoring practices for patients receiving opioid analgesia. Moreover, there is a paucity of information and no consensus about the benefits of technology-supported monitoring, such as pulse oximetry (measuring oxygen saturation) and capnography (measuring end-tidal carbon dioxide), in hospitalized patients receiving opioids for pain therapy. To date, there have not been any randomized clinical trials to establish the value of technologic monitoring in preventing adverse respiratory events. Additionally, the use of technology-supported monitoring is costly, with far-reaching implications for hospital and nursing practices. As a result, there are considerable variations in screening for risk and monitoring practices. All of these factors prompted the American Society for Pain Management Nursing to approve the formation of an expert consensus panel to examine the scientific basis and state of practice for assessment and monitoring practices for adult hospitalized patients receiving opioid analgesics for pain control and to propose recommendations for patient care, education, and systems-level changes that promote quality care and patient safety., (Copyright © 2011 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Background: A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours., Patients and Methods: To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail., Results: Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians., Conclusions: A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients., Patients and Methods: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included oxaliplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, every 21 days., Results: All the 24 patients were evaluable for response and toxicity. According to RECIST criteria we observed one complete response and 11 partial responses for an overall response rate of 50%. Overall survival for all the patients on study was 12 months (range 2-30). According to WHO criteria, three patients (12.5%) suffered grade 3 neutropenia and three patients (12.5%) grade 3 thrombocytopenia. Only two patients (8%) suffered grade 3 neuropathy., Conclusions: Oxaliplatin and gemcitabine chemotherapy seems to be effective with a favorable safety profile in first-line chemotherapy of advanced biliary tract cancers.