Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3\',5\'-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase DNA integrity scanning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of disA was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in Actinobacteria and thus the global control of cellular physiology.IMPORTANCESince the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium Saccharopolyspora erythraea as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased disA expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis.

Formalin is the international gold-standard fixative in pathology laboratories. However it is not the ideal one considering its deleterious effects on individuals and the environment. Complete formalin removal or even substitution does not seem possible in the near future. In this update, we present various tools allowing to integrate the use of formalin into an ecocare approach. Among them, formalin recycling according to the protocol developed by the University Hospital of Bordeaux is simple to implement and delivers rapid and significant results, allowing pathology professionals to meet the sustainable development objectives included in the France 2030 agenda.

UNASSIGNED: Advance care planning (ACP) is a process that involves patients expressing their personal goals, values, and future medical care preferences. Digital applications may help facilitate this process, though their use in older adults has not been adequately studied.
UNASSIGNED: This pilot study aimed to evaluate the reach, adoption, and usability of Koda Health, a web-based patient-facing ACP platform, among older adults.
UNASSIGNED: Older adults (aged 50 years and older) who had an active Epic MyChart account at an academic health care system in North Carolina were recruited to participate. A total of 2850 electronic invitations were sent through MyChart accounts with an embedded hyperlink to the Koda platform. Participants who agreed to participate were asked to complete pre- and posttest surveys before and after navigating through the Koda Health platform. Primary outcomes were reach, adoption, and System Usability Scale (SUS) scores. Exploratory outcomes included ACP knowledge and readiness.
UNASSIGNED: A total of 161 participants enrolled in the study and created an account on the platform (age: mean 63, SD 9.3 years), with 80% (129/161) of these participants going on to complete all steps of the intervention, thereby generating an advance directive. Participants reported minimal difficulty in using the Koda platform, with an overall SUS score of 76.2. Additionally, knowledge of ACP (eg, mean increase from 3.2 to 4.2 on 5-point scale; P<.001) and readiness (eg, mean increase from 2.6 to 3.2 on readiness to discuss ACP with health care provider; P<.001) significantly increased from before to after the intervention.
UNASSIGNED: This study demonstrated that the Koda Health platform is feasible, had above-average usability, and improved ACP documentation of preferences in older adults. Our findings indicate that web-based health tools like Koda may help older individuals learn about and feel more comfortable with ACP while potentially facilitating greater engagement in care planning.

Acute canine polyradiculoneuritis (ACP) is a common peripheral neuropathy in dogs, and is generally self-limiting and benign. Electrodiagnostic (EDX) tests are typically performed after 7-10 days. Delaying the definitive diagnosis may hamper the treatment of other causes of acute weakness, which may require specific treatments and may carry different prognoses. This retrospective multicenter study aims to assess whether EDX performed within the first 6 days of clinical signs onset can detect alterations indicative of ACP, and aims to characterize the most prevalent alterations. A total of 71 dogs with suspected ACP were retrospectively analyzed and classified into two groups based on EDX timing: early group (EG, 1-6 days after symptom onset) and late group (LG, 7-15 days after symptom onset). In our study, no significant differences were found between the two groups in motor nerve conduction studies (MNCSs) and F-wave analysis, indicating that EDX is able to demonstrate abnormalities even in the first 6 days from onset. Although the LG showed significantly greater degrees of electromyographic (EMG) alterations compared to the EG, frequent muscle alterations were still observed in the EG group. These findings support the use of EDX in patients with suspected ACP within the first 6 days from the clinical onset. Prompt neurophysiological examinations for suspected ACP patients can be performed effectively and can help allow for early diagnosis and facilitate appropriate treatment.

BACKGROUND: Research evidence suggests that a lack of engagement with palliative care and advance care planning could be attributed to a lack of knowledge, presence of misconceptions and stigma within the general public. However, the importance of how death, dying and bereavement are viewed and experienced has been highlighted as an important aspect in enabling public health approaches to palliative care. Therefore, research which explores the public views on strategies to facilitate engagement with palliative care and advance care planning is required.
METHODS: Exploratory, qualitative design, utilising purposive random sampling from a database of participants involved in a larger mixed methods study. Online semi-structured interviews were conducted (n = 28) and analysed using reflexive thematic analysis. Thematic findings were mapped to the social-ecological model framework to provide a holistic understanding of public behaviours in relation to palliative care and advance care planning engagement.
RESULTS: Three themes were generated from the data: \"Visibility and relatability\"; \"Embedding opportunities for engagement into everyday life\"; \"Societal and cultural barriers to open discussion\". Evidence of interaction across all five social ecological model levels was identified across the themes, suggesting a multi-level public health approach incorporating individual, social, structural and cultural aspects is required for effective public engagement.
CONCLUSIONS: Public views around potential strategies for effective engagement in palliative care and advance care planning services were found to be multifaceted. Participants suggested an increase in visibility within the public domain to be a significant area of consideration. Additionally, enhancing opportunities for the public to engage in palliative care and advance care planning within everyday life, such as education within schools, is suggested to improve death literacy and reduce stigma. For effective communication, socio-cultural aspects need to be explored when developing strategies for engagement with all members of society.

The primary objective of this study is to record the clinical outcomes of autologous conditioned plasma (ACP) for the treatment of knee osteoarthritis (OA) based on published literature. Multiple databases (PubMed, Embase, Web of Science and Scopus) were searched using terms for \"knee OA\" and the intervention \"ACP\" for articles published in English to January 4, 2024. All clinical studies using ACP for knee OA were included. Studies not utilizing ACP alone, i.e. used as an adjunct with other modalities or not focusing on the management of knee OA, were excluded. Five studies, three randomized controlled trials (RCTs) and two real-world post-market studies conducted in a clinical practice met the inclusion/exclusion criteria and were included in this study. All studies demonstrated statistically significant improvements in various patient-reported outcome measures (PROMs), however the studies performed in the clinical practice reported non-accomplishment of minimally clinically important difference (MCID). The results demonstrated the potential of ACP for management of knee OA, however the MCID was not achieved in real-world clinical settings. Thus, more adequately powered RCTs with longer follow-up as well as real-world post-market studies are warranted to establish long-term efficacy and justify routine clinical use, respectively, of ACP in patients suffering with knee OA.

Huanglongbing (HLB) is a fatal citrus disease that is currently threatening citrus varieties worldwide. One putative causative agent, Candidatus Liberibacter asiaticus (CLas), is vectored by Diaphorina citri, known as the Asian citrus psyllid (ACP). Understanding the details of CLas infection in HLB disease has been hindered by its Candidatus nature and the inability to confidently detect it in diseased trees during the asymptomatic stage. To identify early changes in citrus metabolism in response to inoculation of CLas using its natural psyllid vector, leaves from Madam Vinous sweet orange (Citrus sinensis (L.) Osbeck) trees were exposed to CLas-positive ACP or CLas-negative ACP and longitudinally analyzed using transcriptomics (RNA sequencing), proteomics (liquid chromatography-tandem mass spectrometry; data available in Dryad: 10.25338/B83H1Z), and metabolomics (proton nuclear magnetic resonance). At 4 weeks postexposure (wpe) to psyllids, the initial HLB plant response was primarily to the ACP and, to a lesser extent, the presence or absence of CLas. Additionally, analysis of 4, 8, 12, and 16 wpe identified 17 genes and one protein as consistently differentially expressed between leaves exposed to CLas-positive ACP versus CLas-negative ACP. This study informs identification of early detection molecular targets and contributes to a broader understanding of vector-transmitted plant pathogen interactions.

UNASSIGNED: Changes in the health care delivery system have altered the way internal medicine (IM) is practiced, with inclusion of subspecialty advanced care practitioners (ACPs) as vital members of the health care team.
UNASSIGNED: ACPs are provided the clinical settings and educational resources within an academic center to become competent in recognizing and managing common and complicated infectious diseases (ID). The ID ACP will be given progressive responsibility with expectations for achievement of milestones as they develop into competent practitioners. We seek to ensure quality, cost-effective, and comprehensive patient-centered care on the ID service in the inpatient and ambulatory settings in compliance with national standards and scope of practice recommendations and regulations.
UNASSIGNED: In recognition of the expanding role of ACPs, we developed a curriculum and guidelines in the subspecialty of ID.
UNASSIGNED: Our proposal greatly adds to the available literature for ACPs to provide the full spectrum of ID practice.

BACKGROUND: Advance care planning (ACP) is becoming increasingly important in medical care. Some suggest standardized approaches to initiate ACP with all older adults. However, the idea of patient-centered care suggests more nuanced approaches tailored to individual older adults\' needs. This study investigated how older adults with different views and needs about ACP can be approached in an adequate and most beneficial way by health care professionals.
METHODS: We used questionnaires, interviews, focus groups and informal conversations with older adults, living in their own homes, who volunteered to take part in our research. The research was participatory as we collaborated closely with practice partners and we used the obtained findings immediately and continuously to inform the next steps of our research throughout the process.
RESULTS: We identified three subgroups of older adults with differential needs regarding ACP-related activities: The first group avoids talking about their needs and wishes for care towards the end of life. These older people benefit from activities, which aim at motivating them to concern themselves with ACP-related topics. The second group consists of older adults who are in principle open for ACP-conversations but do not initiate these themselves. This group either trusts their next-of-kin or their healthcare professional to act in accordance with their wishes or does not bring up the topic in order to avoid confronting relevant others with possibly unpleasant topics. This group of people benefits from information about ACP and from healthcare professionals initiating the ACP process. The third group of older people initiates the ACP process themselves, gathers information, and takes the necessary steps for ACP. With this group it remains relevant to check carefully whether they have indeed taken all relevant steps and shared the information with all relevant involved care institutions and relatives.
CONCLUSIONS: We propose a model to simplify adjustments of ACP to individuals\' needs. Our suggested approach might contribute to increasing the motivation of older people to engage in ACP conversations if these are more closely related to their own needs. Further, it might also contribute to simplifying the individual shaping of the ACP process for healthcare professionals as our suggested model offers clear guidance for approaching different types of older people in different ways. The suggested approach may in future be used for training health care professionals in the conduct of ACP conversations.

Benefit from the strong coordination property, lanthanide metal ions have been used as competitive reagents to modulate the fluorescence changes of the system. However, lanthanide metal ions as inducers for aggregation-induced emission enhancement in nanosystems is rare. Herein, we report a \"turn on-off-on\" fluorescent switch for cascade detection of acid phosphatase (ACP) and adenosine triphosphate (ATP) based on the competitive coordination of samarium ions (Sm3+). Novel copper nanoclusters (CuNCs) with long wavelength emission (614 nm) stabilized by glutathione (GSH) and glycylglycine (Gly-Gly) have been confirmed to have AIE property. With the continuous aggregation of GSH/Gly-Gly CuNCs under the induction of Sm3+, the fluorescence of the system increased to achieve the \"turn-on\" process. The coordinated behaviour between Sm3+ and GSH/Gly-Gly CuNCs is discussed. Due to the strong metal coordination ability of ATP, the Sm3+ coordinated with the GSH/Gly-Gly CuNCs is competed out, resulting in the fluorescence \"turn-off\" process of the system. As the substrate of enzymatic hydrolysis of ACP, with the continuous hydrolysis of ATP by ACP, Sm3+ coordinates with GSH/Gly-Gly CuNCs again, which leads to the AIE effect and realize the fluorescence \"turn-on\" process of the system. This strategy results in ATP linear range of 0.508 ~ 120.0 μM with a detection limit of 0.508 μM (S/N = 3) and ACP linear range of 0.011 ~ 30.0 U·L-1 with a detection limit of 0.011 U·L-1 (S/N = 3). Application to biologic samples was successful.