Van London Co.

Background Patients with AKI experience higher rates of heart failure (HF). This study seeks to identify criteria to assess the risk of heart failure post-hospitalization, with a special focus on AKI patients. We hypothesized that the combined use of 9 vascular biomarkers would predict future heart failure events after AKI. Using a study of 1497 hospitalized patients with and without AKI, we found that these 9 vascular biomarkers successfully stratified patients into different risk groups for HF, and were able to improve prediction of HF when added to routine clinical variables. Methods Using the ASSESS-AKI cohort, we performed an unsupervised spectral cluster analysis with 9 plasma biomarkers measured at 3 months post-hospitalization [Angiopoietin (angpt)-1, angpt-2, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-d, VEGF receptor 1 (R1), solubleTie-2 (sTie-2), placental growth factor (PlGF), and basic fibroblast growth factor (bFGF)] in 1,497 patients, half of whom had AKI. We used a Cox regression analysis to evaluate the associations between the clusters and HF. Models were adjusted for demographics, cardiovascular disease risk factors, medications, ICU status, lung disease, sepsis, clinical center, and 3-month post-discharge serum creatinine and proteinuria. We calculated change in the area under the curve (AUC) for the prediction of HF or death at 3 years by adding the biomarkers to a clinical model selected by a penalized regression with LASSO. We also calculated a net reclassification index for the addition of the biomarkers to the clinical model. Results Three biomarker-derived clusters were identified: Cluster 1 [n = 302, Vascular Injury (Injury) Phenotype] had higher levels of injury markers, whereas Cluster 2 [n = 728, Vascular Repair (Repair) Phenotype] had higher levels of repair markers. Cluster 3 (n = 467) had lower levels of all markers (Dormant Phenotype). Across the entire cohort, those with the Injury Phenotype had twofold higher risk of a HF event compared to the Repair Phenotype [aHR 2.24 (95% CI: 1.57–3.19)] and noted in both participants with AKI [aHR 2.12 (95% CI: 1.35–3.34)] and without AKI [aHR 2.94 (95%CI: 1.57–5.50)]. The Dormant Phenotype was associated with higher risk of HF events only in participants without AKI. The AUC for the prediction of HF event or death at 3 years by the biomarkers was 0.76 (95% CI: 0.73–0.80), 0.77 (95% CI: 0.73–0.80) for the clinical model, and 0.80 (95% CI: 0.77–0.83) for the combined model. The addition of the biomarkers significantly improved reclassification of HF event or death. Conclusions Vascular biomarkers can be used to derive phenotypes capable of stratifying future risk of HF events in recently hospitalized patients with or without AKI.

Background The monoamine system, particularly the serotonergic neurons in the dorsal raphe nucleus (DRN), associated with the synthesis and release of 5-hydroxytryptamine, is crucial for regulating pain. The lateral habenula (LHb) modulates DRN neurons by acting through GABAergic neurons located in the rostromedial tegmental nucleus (RMTg). However, the role of RMTg in mediating the LHb and regulating pain remains unclear. Thus, we aimed to assess the role of the LHb-RMTg pathway in inflammatory pain. Methods Male C57BL/6 mice were used in the chemogenetic experiments, while male and female Vglut2-ires-cre mice were used in the optogenetic experiments; in both experiments, inflammatory pain model and control groups were established. We performed the Hargreaves and Von Frey tests to assess nociceptive behavior as well as immunohistochemistry staining after chemogenetic activation experiments. Statistical analyses were performed using a t-test, one-way analysis of variance (normally distributed data) or Kruskal–Wallis test (non-normally distributed data) and two-way analysis of variance. Results Chemogenetic activation/inhibition of RMTg-projecting LHb excitatory neurons was sufficient to decrease or increase heat sensitivity thresholds. Additionally, inhibition of the LHb-RMTg circuit reversed the decreased heat sensitivity thresholds under inflammatory pain conditions using chemogenetic and optogenetic approaches. However, this circuit did not affect mechanical allodynia thresholds, and chemogenetic activation of the circuit decreased c-Fos immunoreactivity in the DRN. Conclusions Our results indicate that activating glutamatergic neurons within the LHb heightens pain sensitivity by triggering GABAergic neurons in the RMTg, which in turn influences neuronal activity in the DRN. This research offers fresh perspectives on the pain mechanism, potentially revealing new therapeutic avenues for managing inflammatory pain. Graphical Abstract

Background Systematic reviews provide the best quality evidence about the effectiveness of health treatments. However, systematic reviews and the important role they play in healthcare are not well understood beyond the walls of academia and healthcare. Systematic reviews can help the public make more informed health choices, based on the best available evidence. The People’s Review aims to provide an opportunity to members of the public to plan and complete a full systematic review online in a supportive and engaging manner. It will be a learning-by-doing experience to support the public’s understanding of what reviews are, how they are done, why they matter, and how they can be used to support everyday health decisions. Methods In The People’s Review the public will conduct a full systematic review, deciding the review question, planning the review, working on the parts of the review, and deciding how to share the review findings, in a ‘learning by doing’ process. The review will be conducted online in eight stages using Cochrane Crowd, an existing citizen science platform. The team working behind-the-scenes of The People’s Review will design, produce, and share learning material to support the public’s understanding at each stage of the review. Discussion Involving the public in a systematic review online will enable members of the public to understand and use systematic reviews in everyday health choices. It provides the public with a unique ‘learning by doing’ opportunity to get to grips with what systematic reviews are and how they are produced. This article describes how we plan to involve the public in The People’s Review. It is not a protocol for the systematic review itself – this will be published separately once the project has commenced, and the public have decided the review question.

Unidentified human remains are frequently found in missing person cases, necessitating identification for forensic purposes and to inform the next of kin. Traditional postmortem fingerprinting methods depend on intact surface fingerprints, which are often compromised by decomposition. A viable alternative is to use internal fingerprints (a blueprint of the surface fingerprint located just below the epidermis) instead. This study assessed the utility of Optical Coherence Tomography (OCT) as a means to record internal fingerprints from excavated human fingers. Conducted at the Amsterdam human taphonomic test site, the investigation comprised two longitudinal studies and two in situ burial scenarios. Human fingers were buried, excavated, and scanned using OCT at various time intervals. Internal fingerprints could be recorded up to 7 days longer than surface fingerprints, with a maximum of 10 days post-burial. These internal fingerprints provided higher minutiae counts, suitable for Automated Fingerprint Identification System (AFIS) searches. Additionally, in one case, fingerprints were successfully extracted after 13 weeks and 10 months of in situ burial. This demonstrates OCT’s potential to enhance postmortem fingerprinting for identifying human remains in forensic investigations.

Forensic taphonomy is the study of postmortem changes of human remains for the purpose of answering legal investigative questions. Many variables can affect the pattern and rate of decomposition of remains, posing challenges for taphonomic studies and estimation of the postmortem interval. Given the gap in knowledge regarding the suitability of using frozen remains to extrapolate conclusions to fresh material, investigating the effects of freeze-thaw cycles followed by burial on human remains is vital for forensic practice and taphonomic research. This study explored the impact of a freeze-thaw cycle and subsequent burial on human tissue decomposition under semi-controlled field conditions. Fresh and fresh-frozen-thawed hands were buried at the Amsterdam Research Initiative for Sub-surface Taphonomy and Anthropology for 31.7 to 340.4 accumulated degree days. Decomposition was assessed using fluorescence measurements targeting protein and fluorescent oxidation products, and broader excitation-emission matrix measurements in skin, adipose, and muscle tissue. Decomposition trends varied primarily by treatment group: fresh samples generally aligned with expectations that protein levels would decrease over time while fluorescent oxidation products increased, whereas fresh-frozen samples deviated significantly from these expectations. Significant differences were found between protein and fluorescent oxidation products levels of fresh and fresh-frozen tissue at corresponding time points, indicating this method’s potential in determining sample state. However, fluorophore peak monitoring in excitation-emission matrices did not prove useful in establishing decomposition trends or potentially distinguishing between sample states. Despite limitations inherent to pilot and human taphonomy studies, this study clearly demonstrates that differences exist in the decomposition of fresh and fresh-frozen tissue, and that these trends vary slightly by tissue type. We therefore conclude that frozen material cannot be considered a proper substitute for fresh tissue regarding taphonomic processes, and the methods used in this study show promise in being used to differentiate between pre-decomposition treatments.

Introduction Analysis of a single tooth and nail can provide valuable forensic information, including year of birth, year of death, age, sex, DNA-profile, geographic residence during childhood and at time of death and drug exposure. The aim is to minimize the amount of used bodily material and to validate the applicability of a multidisciplinary sampling protocol. Methods A nail of the big toe, a tooth and blood of seven deceased individuals were collected postmortem. Collected materials were sampled and segmented in accordance with the multidisciplinary sampling protocol. DNA analysis was conducted on the pulp of the tooth, isotope analysis (Sr, Pb, O and C) on the enamel and ¹⁴C-, toxicological and tooth cementum annulation analysis on root segments. DNA-, isotope (Sr, Pb, O and C) -, toxicological-, and ¹⁴C -analysis were conducted on toenail segments. The acquired DNA profiles were compared with profiles acquired from blood. Results Material from seven deceased persons was analysed. 45 out of 56 analyses on dental samples were successful, constituting a success rate of 80%. Additionally, 27 out of 35 analyses were successful on nail samples, yielding a success rate of 77%. DNA-, toxicological and ¹⁴C- analyses performed better in nail than in tooth. Isotope analyses performed better in tooth than in nail. A profile with personal characteristics was constructed and matched for 62% of parameters with collected medical information. Conclusion The performed sampling protocol for simultaneous multidisciplinary forensic analysis on a single tooth and nail sample provided applicable results and valuable information.

Background Mild hypoxic ischemic encephalopathy is associated with sub optimal cognition and learning difficulties at school age. Although whole-body hypothermia reduces death and disability after moderate or severe encephalopathy in high-income countries, the safety and efficacy of hypothermia in mild encephalopathy is not known. The cooling in mild encephalopathy (COMET) trial will examine if whole-body hypothermia improves cognitive development of neonates with mild encephalopathy. Methods The COMET trial is a phase III multicentre open label two-arm randomised controlled trial with masked outcome assessments. A total of 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over 2 ½ years following parental consent. The neonates will be randomised to 72 h of whole-body hypothermia (33.5 ± 0.5 C) or normothermia (37.0 ± 0.5 C) within six hours or age. Prior to the recruitment front line clinical staff will be trained and certified on expanded modified Sarnat staging for encephalopathy. The neurological assessment of all screened and recruited cases will be video recorded and centrally assessed for quality assurance. If recruitment occurs at a non-cooling centre, neonates in both arms will be transferred to a cooling centre for continued care, after randomisation. All neonates will have continuous amplitude integrated electroencephalography (aEEG) at least for the first 48 h to monitor for seizures. Predefined safety outcomes will be documented, and data collected to assess resource utilization of health care. A central team masked to trial group allocation will assess neurodevelopmental outcomes at 2 years of age. The primary outcome is mean difference in composite cognitive scores on Bayley scales of Infant and Toddler development 4th Edition. Discussion The COMET trial will establish the safety and efficacy of whole-body hypothermia for mild hypoxic ischaemic encephalopathy and inform national and international guidelines in high income countries. It will also provide an economic assessment of whole-body hypothermia therapy for mild encephalopathy in the NHS on cost-effectiveness grounds. Trial registration number NCT05889507 June 5, 2023.

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.

The safety of persons with intellectual and developmental disabilities (IDD) and their care providers is a priority within human services settings. Because there is an increased risk for injury competency-based training must be provided to care providers so they know how to, and can, implement safety protocols effectively. Once training has been provided, supervisors should assess generalization of care provider performance in the natural environment. Additionally, frequent observations of care provider performance should be scheduled to ensure maintenance of safety protocols. Should supervisory observations reveal performance drift, it is the supervisor’s responsibility to provide refresher training or some other intervention to improve performance to high levels of integrity. Without this level of analysis and support, we cannot ensure that persons with IDD and their care providers will be safe in their educational, treatment, and habilitation settings.

This article seeks to complement efforts to summarize information on the exceptional natural significance of the Emperor Seamounts. The human history of the Emperor Seamounts is culturally diverse and spans thousands of years. This ranges from indigenous cultures to the period of European colonial exploration and expansion to the rise of the modern global economy and its impact on the area through the hunting of marine mammals, fishing, and the transportation of commodities across these remote waters on ships. Some of these vessels were wrecked or disappeared, and may rest on the seabed of the Emperor Seamounts. Understanding this human history is critical in approaching the assessment, ongoing study, public outreach and management of this remote region, which has been highlighted as one of the most important areas beyond national jurisdiction to protect globally.

Private sector investable assets totalling USD 35.3 trillion globally are currently bound by at least one environmental, social and governance (ESG) criterion, ¹ and could be targeted to deliver responses to the environmental crisis and subsequent devastating impact on vulnerable communities. However private sector finance for climate resilience and nature recovery is reported to be either moving very slowly, or not at all. ² So what is the hold up? The co-founders of Biodiversity Capital have a longstanding combined history of delivering projects in urban regeneration, as well as green ³ and blue ⁴ infrastructure, housing and culture across the private and public sector, where financing for projects follows a linear start to finish model with handover to the client on completion. Since the beginning of the 20 th century, charities have received funding from either government or philanthropists to deliver programmes against an agreed set of quantifiable targets and outputs. The current crisis on our hands is not static, it is a mix of complex, intertwined social, economic and environmental factors, where long-term stewardship, ultimately unique and very local, is now deemed a fundamental part of the equation from the start. In the light of this, we argue that achieving climate justice will require private finance to embrace the distinctive nature of collaboration between governments and the non-profit sector.

Introduction The risk of harm associated with living within 10 km of industrial wind turbines (IWTs) is unresolved and continues to be debated internationally. While sources such as judicial proceedings, scientific literature, social media, and Internet websites report that some neighbors contemplate leaving their homes, research on this topic is limited. This study continues to explore why they contemplated such a housing decision. Methodology The ethics-reviewed study used the qualitative Grounded Theory (GT) methodology and interviewed 67 consenting participants, 18 years or older, who had previously lived, or were currently living, within 10 km of IWTs. Audio files were transcribed to text and the data were coded and analyzed using NVivo Pro (v. 12.6) software. Objectives The objective of this manuscript is to explore participants’ descriptions of their medical diagnoses provided by their physicians and physician specialists. Results Data analysis revealed primary and subthemes associated with environmental interference and altered living conditions. Of the 67 participants, eight described their diagnoses of medical conditions as given by their physicians and physician specialists. Descriptions of conversations with participants’ health-care providers were also surveyed. Discussion Medical diagnoses, descriptions of comments by health practitioners and the commonality of globally reported adverse health effects (AHEs), support the potential risk of locating IWTs near residential areas. It is recommended that members of the public, government authorities, policy makers, researchers, health practitioners, and social scientists with an interest in health policy and disease prevention acknowledge this risk and advocate for the immediate, effective, and timely resolution for affected neighbors. Conclusions The GT methodology was used to develop a substantive theory regarding the housing decisions of participants living within 10 km of a Wind Power Plant. Results from the interviews indicate that these decisions were motivated by the potential for, or the experience of, AHEs which they attributed to living in proximity to these installations.