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Background Nurse care managers (NCM) operate through care management programs to provide care for persons living with dementia (PLWD) and interact regularly with their family caregivers; however, most do not receive formal instruction in dementia care or caregiver support. CRESCENT (CaReEcoSystem primary Care Embedded demeNtia Treatment) is a telephone-based dementia care intervention adapted from the Care EcoSystem model designed to equip NCMs with these tools. For this study, we aimed to measure intervention fidelity and understand how dementia care training impacted NCMs’ provision of dementia care management services during interactions with caregivers of PLWD. Methods We recruited 30 active NCMs; 15 were randomly assigned to receive training. For each nurse, we randomly selected 1–3 patients with a diagnosis of dementia in each nurse’s care during January-June 2021 for a total of 54 medical charts. To assess training uptake and fidelity, we identified documentation by NCMs of CRESCENT protocol implementation in the medical records. To understand how the training impacted the amount and types of dementia care management services provided in interactions with family caregivers, we compared attention to key dementia topic areas between trained NCMs (intervention) and untrained NCMs (control). Results Within the trained group only, community resources for PLWD, followed by safety, medication reconciliation, and advanced care planning topic areas were addressed most frequently (> 30%), while behavior management was addressed least frequently (12%). Trained NCMs were more likely to document addressing aspects of caregiver wellbeing (p = 0.03), community resources (p = 0.002), and identification of behavior (p = 0.03) and safety issues (p = 0.02) compared to those without training. There was no difference between groups in the amount of care coordination provided (p = 0.64). Conclusion Results from this study demonstrate that focused dementia care training enriches care conversations in important topic areas for PLWD and family caregivers. Future research will clarify how best to sustain and optimize high quality dementia care in care management programs with special attention to the NCM-family caregiver relationship. Trial number NCT04556097.

Cancer is a leading cause of death throughout the world. Melanoma is a skin cancer with a significant impact on global public health. Application of nanotechnology in the field of cancer diagnosis, drug delivery, imaging and therapy, has the most attractive approach as nanoparticles reach target sites easily due to their unique properties. Previous studies have shown that titanium dioxide nanotubes (TNT) and quercetin are effective anticancer agents. However, conjugated TNT with quercetin (TNT–Qu) as a combinational treatment is unexplored yet. This study is aimed to explore the anticancer activity of TNT, quercetin, and TNT–Qu in B16F10 melanoma skin cancer cells. TNT–Qu significantly inhibited proliferation at 25 µg/mL of IC 50 lower than quercetin (34 µg/mL) and TNT alone (72 µg/mL). TNT–Qu treatment inhibited migration and significantly induced 60.29% apoptosis in melanoma cells when compared to TNT (14.14%) or quercetin (44.86%) alone treatment. Furthermore, quercetin and TNT–Qu decreased the reactive oxygen species and superoxide levels due to quercetin's antioxidant properties. TNT–Qu treatment arrested 55.5% cells in G2/M phase more than quercetin (30.7%) or pristine TNT (3.7%) treatment. The molecular mechanism of TNT–Qu on melanoma cells revealed that it enhanced the cleaved caspase-3 levels and induced more apoptosis than TNT or quercetin alone. Hence, Novel TNT–Qu exhibited enhanced anticancer properties and could be a potential therapeutic combinational molecule for the treatment of skin cancer. Schematic representation of the proposed mechanism of TNT, quercetin and TNT–Qu inducing apoptosis in B16F10 melanoma cells. TNT–Qu enhanced the cleaved caspase-3 and induced caspase-dependent apoptosis. Importantly, it down-regulates the ROS and dysfunctions mitochondria and enhances the DNA fragmentation.

There is a paucity of data on use of dexmedetomidine as a sedative agent in mechanically ventilated children. To compare the efficacy of dexmedetomidine and midazolam for sedation in mechanically ventilated children aged 1 month — 15 years. Secondary objectives were to compare the need for top-up doses of fentanyl and paralytic agents, duration of mechanical ventilation, ICU stay and hospital stay, and adverse events. Open label, non-inferiority, randomized controlled trial. PICU of a tertiary care teaching hospital in India. Consecutive children aged 1 month to 15 years who were mechanically ventilated. Children were randomized to either dexmedetomidine or midazolam and the doses were titrated to maintain target sedation score of 4 or 5 as measured by Penn State Children Hospital Sedation algorithm. The percentage of time spent in level 4 or 5 of Penn State Children Hospital sedation algorithm for ventilated children. 49 children were randomized (24 to ‘midazolam group’ and 25 to ‘dexmedetomidine group’). There was no difference in the percentage of time spent in the targeted sedation between the groups [midazolam 67.3% (18.8) vs. dexmedetomidine 56.3 %. (28.6); P=0.12]. The absolute difference in the percentage of time spent was −10.9% [SE (95% CI) 7.05: (−25.15 to 3.25)]. The lower end of 95% CI for the difference breached the non-inferiority limit of −20%. Number of fentanyl boluses, duration of mechanical ventilation, ICU stay, and hospital stay were similar. Four (17.4%) children in dexmedetomidine group developed persistent bradycardia. Non-inferiority of dexmedetomidine compared to midazolam for sedation in children on mechanical ventilation could not be established.

In critically ill patients, deserving extracorporeal membrane oxygenation (ECMO), choosing the right pattern of cannulation such as veno-venous (VV), veno-arterial (VA), veno-veno-arterial (VVA), and central; selecting the appropriate size cannulae; and good cannulation techniques are all pre-requisites for the successful outcome of ECMO. We are describing the selection criteria for choosing appropriate size cannulae, cannulation configurations, available cannulae, and possible complications. A brief note on anticoagulation was added.

The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) – when conjugated to the carrier protein, keyhole limpet hemocyanin (KLH) – to be capable of inducing broadly neutralizing responses against HIV-1 in animal models. However, KLH is a multi-subunit particle derived from a natural source, and its manufacture as a clinical product remains a challenge. Here we report the preclinical development of recombinant tetanus toxoid heavy chain fragment (rTTHC) linked to FP8 (FP8-rTTHC) as a suitable FP-conjugate vaccine immunogen. We assessed 16 conjugates, made by coupling the 4 most prevalent FP8 sequences with 4 carrier proteins: the aforementioned KLH and rTTHC; the H. influenzae protein D (HiD); and the cross-reactive material from diphtheria toxin (CRM197). While each of the 16 FP8-carrier conjugates could elicit HIV-1-neutralizing responses, rTTHC conjugates induced higher FP-directed responses overall. A Sulfo-SIAB linker yielded superior results over an SM(PEG)2 linker but combinations of carriers, conjugation ratio of peptide to carrier, or choice of adjuvant (Adjuplex or Alum) did not significantly impact elicited FP-directed neutralizing responses in mice. Overall, SIAB-linked FP8-rTTHC appears to be a promising vaccine candidate for advancing to clinical assessment.

The aim of this study is to describe a less aggressive approach to management of positive nipple margin following nipple-sparing mastectomy (NSM), allowing for preservation of the nipple–areolar complex (NAC). A single-institution retrospective chart review was performed for patients undergoing NSM from 1989 to 2017. Positive nipple margin was defined as any residual invasive carcinoma or ductal carcinoma in situ (DCIS) within the additional nipple margin. Management included complete NAC removal, subareolar shave biopsy, or observation alone. Primary outcomes included rates of positive nipple margin and local recurrence. A total of 819 breasts underwent NSM, yielding a total of 32 breasts (3.9%) with positive nipple margin. Management included 11 (34.4%) subareolar shave biopsies, 15 (46.9%) complete NAC excisions, and 5 (15.6%) with observation alone, plus 1 (3.1%) lost to follow-up. Final pathology after subareolar shave biopsy did not reveal any residual disease, and no patients developed NAC necrosis or required NAC removal. Final pathology after NAC excision revealed 3 of 15 with additional disease (1 invasive ductal carcinoma, 2 DCIS). Of the five patients who had no subsequent intervention, tumor pathology was DCIS in all cases. One patient received adjuvant radiation therapy. Mean time to intervention was 3.7 ± 1.9 with mean follow-up of 2.9 years. Management of positive nipple margin after NSM with subareolar shave biopsy is a safe alternative to preserve the NAC.

Textile production industry is one of the biggest industries available and it is known by its negative effects to the environment. Greenhouse gas emissions can drastically be reduced by just recycling the textile waste. Such textile recycling has become a lot easier with clothing retailers now starting to offer recycling checkpoints. Moreover, people today are often challenged by overloaded wardrobes and store many clothing items that they never use. In this paper, we describe an Internet of Things system that creates incentives for the users to recycle their clothes, benefiting the environmental sustainability. We propose a content-based recommendation approach that utilizes semantic web technologies and that leverages a set of context signals obtained from the system’s architecture, to recommend clothing items that might be relevant for the user to recycle. Experiments on a real-world dataset show that our proposed approach outperforms a baseline which does not utilize semantic web technologies.

Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-κB signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-κB inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome.

To compare patient outcomes using the Pediatric Index of Mortality-3 (PIM-3) model with PIM-2 model for children admitted to the intensive care unit. We prospectively recorded the baseline characteristics, variables of PIM-3 and PIM-2 at admission, and outcomes of children ≤17 years over a period of 11 months. We used Area Under Receiver Operating Characteristics (AU-ROC) curves and Goodness-of-fit (GOF) tests to determine which of the two models had better discrimination and calibration. Out of 202 children enrolled, 69 (34%) died. Sepsis and pneumonia were the common admitting diagnoses. The AU-ROC was better for PIM-3 (0.75) as compared to PIM-2 (0.69; P=0.001). The GOF-P value was 0.001 for both models, that indicated poor calibration of both (P

Many of today’s online news websites and aggregator apps have enabled users to publish their opinions without respect to time and place. Existing works on topic-based sentiment analysis of product reviews cannot be applied to online news directly because of the following two reasons: (1) The dynamic nature of news streams require the topic and sentiment analysis model also to be dynamically updated. (2) The user interactions among news comments can easily lead to inaccurate topic extraction and sentiment classification. In this paper, we propose a novel probabilistic generative model (DTSA) to extract topics and the specified sentiments from news streams and analyze their evolution over time simultaneously. In DTSA, three different timescale models are studied to account for the historical dependencies of sentiment-topic word distributions at current epoch, continuous, skip and multiple timescale models. Additionally, we further consider the links among news comments to avoid the error caused by user interactions. In order to mine more interpretable topics, a Conditional Random Fields (CRF) model is adopted to label a set of meaningful phrases for augmenting the bag-of-word features. Finally, we derive distributed online inference procedures to update the model with newly arrived data and show the effectiveness of our proposed model on real-world data sets.

Objectives To describe experience with airway pressure release ventilation (APRV) in children with severe acute respiratory distress syndrome (ARDS) refractory to conventional low tidal volume ventilation. Methods This retrospective observational study was performed in an 11-bed, level 3 pediatric intensive care unit. Evaluation was made of 30 pediatric patients receiving airway pressure release ventilation as rescue therapy for severe ARDS. Results Patients were switched to APRV on an average 3.2 ± 2.6 d following intubation. When changed from conventional mechanical ventilation (CMV) to APRV, there was an expected increase in the SpO2/FiO2 ratio (165.1 ± 13.6 vs. 131.7 ± 10.2; p = 0.035). Mean peak inspiratory pressure was significantly lower during APRV (25.4 ± 1.26 vs. 29.8 ± 0.60, p

Background Multimorbid patients in nursing homes are prescribed long lists of medication, often without sufficient clinical evaluations beforehand. This results in poor clinical effects of the prescribed medication and significant side-effects, especially in patients with impaired cognition. The aim of this paper is to describe the process, content and implementation of a clinical medication review encompassing clinical testing and collegial support to prescribers. Methods The implementation process of a novel approach to medication review in nursing homes was logged thoroughly by structured staff feedback. Staff experienced promotors and barriers to implementation also were collected. The study was part of a cluster randomized controlled trial, in which 36 long-term care units received the COSMOS intervention. Nurses and physicians randomized to the intervention group participated in educational programs, training in clinical evaluation of the patients, and interprofessional medication review with collegial mentoring. Results The intervention group contained 297 patients from 36 nursing home units. There were 105 staff attendees for the education program. The units were served by 21 different physicians. Clinical medication reviews were performed in all units and all patients were assessed prior to the medication reviews. Of the 240 patients with a logged intervention process, 220 (92%) underwent a medication review. The intervention generated enthusiasm and improved communication among nursing staff and between nursing staff and physicians. The interprofessional discussions helped to facilitate difficult decisions pertaining to treatment levels. Reported barriers were lack of time, low engagement of all nursing staff and physicians, and ethical dilemmas. Conclusions Clinical medication reviews were implemented for almost all patients, and every patient was systematically assessed prior to the medication review. The physicians perceived collegial mentoring as an asset, learning from each other facilitated decision making in terms of difficult aspects of prescribing. Knowledge about barriers and promotors can improve implementation of similar interventions in other nursing homes. Trial registration Clinicaltrials.gov (NCT02238652). Registered July 7th 2014.