The role of protein kinase D (PKD) in obesity: Lessons from the heart and other tissues.

Obesity causes a range of tissue dysfunctions that increases the risk for morbidity and mortality. Protein kinase D (PKD) represents a family of stress-activated intracellular signalling proteins that regulate essential processes such as cell proliferation and differentiation, cell survival, and exocytosis. Evidence suggests that PKD regulates the cellular adaptations to the obese environment in metabolically important tissues and drives the development of a variety of diseases. This review explores the role that PKD plays in tissue dysfunction in obesity, with special consideration of the development of obesity-mediated cardiomyopathy, a distinct cardiovascular disease that occurs in the absence of common comorbidities and leads to eventual heart failure and death. The downstream mechanisms mediated by PKD that could contribute to dysfunctions observed in the heart and other metabolically important tissues in obesity, and the predicted cell types involved are discussed to suggest potential targets for the development of therapeutics against obesity-related disease.

The Fulfillment Center Intervention Study: Protocol for a group-randomized control trial of a participatory workplace intervention.

Warehousing and storage is an economically vital industry, with 1.2 million workers in 2020. The Fulfillment Center Intervention Study focuses on workers in fulfillment centers in the e-commerce segment of this industry. Fulfillment centers are a growing yet understudied work environment which provides a unique setting to further examine how working conditions and worker voice influence health. The Study involves a group-randomized controlled trial comparing participants in worksites randomized to launch the participatory intervention (Health and Well-Being Committees, or HaWCs) with participants working for the same firm in control sites. HaWCs serve as a new formal voice channel where a small group of frontline workers and supervisors solicit workers' concerns and ideas about safety (e.g., physical hazards), the psychosocial environment (e.g., how workers feel about their treatment at work), and work organization (e.g., workflow, training opportunities, scheduling) and then develop and implement improvement projects in response. The primary objectives of the study are to evaluate the efficacy of the HaWC intervention and its effect on mental health outcomes and changes in the conditions of work within fulfillment centers, and to conduct a process evaluation of key contextual factors that support effective intervention implementation and sustained engagement. To our knowledge, this will be the first trial of a participatory intervention within a fulfillment center setting. Anticipated challenges include competing demands and company initiatives that may limit management support and high turnover. Should the intervention be shown to be feasible, the outcomes from this study will inform future randomized controlled trials of participatory interventions. Trial registration: This trial is registered with the ClinicalTrials.gov registry (NCT05199415) and approved by the Institutional Review Board (IRB) at the Massachusetts Institute of Technology (Protocol: 200800024).

Results of a cognitive behavior therapy-based intervention for antenatal anxiety on birth outcomes in Pakistan: a randomized control trial.

Antenatal anxiety is among the risk factors for adverse birth outcomes, which are common in Pakistan. Between 2019 and 2022, we conducted a randomized controlled trial to evaluate the effects of the Happy Mother-Healthy Baby program, designed to reduce anxiety during pregnancy through use of Cognitive Behavior Therapy, on birth outcomes with 796 women in Rwalpindi, Pakistan. We performed intent-to-treat analysis and per protocol analyses. Intention-to-treat analyses showed no difference in the odds of low birthweight (LBW) (Adj. OR = 0.82, 95% CI 0.55-1.28 p = 0.37), preterm birth (PTB) (Adj. OR = 1.20 95% CI 0.83-1.71, p = 0.33) or small-for-gestational age (SGA) birth, (Adj. OR = 0.76, 95% CI 0.56-1.09, p = 0.16). Among completers who received ≥ 5 intervention sessions, the odds of LBW and SGA were 39% and 32% lower (Adj. OR = 0.61, 95% CI 0.43-0.87, p < 0.01; Adj. OR = 0.68, 95% CI 0.53-0.89, p < 0.01). The significant LBW and SGA results among the intervention completers suggest that the program may be effective when a sufficient dose is received. However, confirmation of these findings is needed due to the fact that randomization is not maintained in completer analyses.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT03880032, 19/03/2019.

Promoting a MOSAIC future in science.

Discoveries at the frontiers of science and finding solutions to pressing biomedical problems will be accelerated when talent, which is widely distributed, is better aligned with opportunities. Strategies to enhance a MOSAIC (Maximizing Opportunities for Scientific and Academic Independent Careers) professoriate and diversify the biomedical landscape are discussed.

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity.

There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer's disease. The role of amyloid beta 42 (Aß42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aß42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aß42. Increasing circulating Aß42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aß40 isoform does not have these same effects on the heart. Administration of an Aß-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aß-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aß42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aß42 inhibits mitochondrial complex I. These data reveal a role for systemic Aß42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer's disease could be effective in combating obesity-induced heart failure.

Assessment of the Diagnostic Accuracy and Reliability of the HEART Score Calculated by Ambulance Nurses Versus Emergency Physicians.

Chest pain is a common complaint for consultation of emergency medical services worldwide. Currently, ambulance nurses (AN) base their decision to transport a patient to the hospital on their own professional experience. The HEART score could improve prehospital risk stratification and patient treatment. The aim of this study is to investigate the interrater reliability and predictive accuracy of the HEART score between AN and emergency physicians (EP). A retrospective analysis on data of 569 patients 18 years and older included in two prehospital HEART score studies. The endpoints are interrater reliability (intraclass correlation [ICC]) and predictive accuracy for major adverse cardiac events within 30 days of the HEART score calculated by AN versus EP. Predictive accuracy is sensitivity, specificity, positive predicted value (PPV) and negative predicted value (NPV). Interrater reliability was good for total HEART score (ICC 0.78; 95% CI 0.75-0.81). However, focusing on the decision to transport a patient, the ICC dropped to 0.62 (95% CI 0.62-0.70). History and Risk factors caused the most variability. Predictive accuracy of HEART differed between AN and EP. The HEART score calculated by AN was sensitivity 91%, specificity 38%, PPV 26%, and NPV 95%. The HEART score calculated by EP was sensitivity 98%, specificity 32%, PPV -26%, and NPV 99%. With a cut-off value of 0-2 for a low HEART score, predictive accuracy significantly improved for the HEART score calculated by AN: sensitivity 98%, specificity 18%, PPV 22%, and NPV 98%. Our study shows a moderate interrater reliability and lower predictive accuracy of a HEART score calculated by AN versus EP. AN underestimate the risk of patients with acute chest pain, with the largest discrepancies in the elements History and Risk factors. Reconsidering the cut-off values of the low-risk HEART category, as well as a carefully developed training program, will possibly lead to a higher interrater reliability of the HEART score and higher predictive accuracy used by AN.

Evolution of a self-renewing, participant-centered workshop series in BMB assessment.

We present as a case study the evolution of a series of participant-centered workshops designed to meet a need in the life sciences education community-the incorporation of best practices in the assessment of student learning. Initially, the ICABL (Inclusive Community for the Assessment of Biochemistry and Molecular Biology/BMB Learning) project arose from a grass-roots effort to develop material for a national exam in biochemistry and molecular biology. ICABL has since evolved into a community of practice in which participants themselves-through extensive peer review and reflection-become integral stakeholders in the workshops. To examine this evolution, this case study begins with a pilot workshop supported by seed funding and thoughtful programmatic assessment, the results of which informed evidence-based changes that, in turn, led to an improved experience for the community. Using participant response data, the case study also reveals critical features for successful workshops, including participant-centered activities and the value of frequent peer review of participants' products. Furthermore, we outline a train-the-trainer model for creating a self-renewing community by bringing new perspectives and voices into an existing core leadership team. This case study, then, offers a blueprint for building a thriving, evolving community of practice that not only serves the needs of individual scientist-educators as they seek to enhance student learning, but also provides a pathway for elevating members to positions of leadership.

Interactions between marine megafauna and plastic pollution in Southeast Asia.

Southeast (SE) Asia is a highly biodiverse region, yet it is also estimated to cumulatively contribute a third of the total global marine plastic pollution. This threat is known to have adverse impacts on marine megafauna, however, understanding of its impacts has recently been highlighted as a priority for research in the region. To address this knowledge gap, a structured literature review was conducted for species of cartilaginous fishes, marine mammals, marine reptiles, and seabirds present in SE Asia, collating cases on a global scale to allow for comparison, coupled with a regional expert elicitation to gather additional published and grey literature cases which would have been omitted during the structured literature review. Of the 380 marine megafauna species present in SE Asia, but also studied elsewhere, we found that 9.1 % and 4.5 % of all publications documenting plastic entanglement (n = 55) and ingestion (n = 291) were conducted in SE Asian countries. At the species level, published cases of entanglement from SE Asian countries were available for 10 % or less of species within each taxonomic group. Additionally, published ingestion cases were available primarily for marine mammals and were lacking entirely for seabirds in the region. The regional expert elicitation led to entanglement and ingestion cases from SE Asian countries being documented in 10 and 15 additional species respectively, highlighting the utility of a broader approach to data synthesis. While the scale of the plastic pollution in SE Asia is of particular concern for marine ecosystems, knowledge of its interactions and impacts on marine megafauna lags behind other areas of the world, even after the inclusion of a regional expert elicitation. Additional funding to help collate baseline data are critically needed to inform policy and solutions towards limiting the interactions of marine megafauna and plastic pollution in SE Asia.

Virtual Reality as Pain Relief in Burn Care: A Pilot Randomized Controlled Trial on the Effectiveness on Pain During Multiple Dressing Changes.

This pilot Randomized Controlled Trial (RCT) aimed to investigate the effectiveness of Virtual Reality (VR)-distraction on pain during multiple Wound Dressing Changes (WDCs). Furthermore, associations between demographic, clinical, and psychological factors and pain during WDC were determined. Participants were randomized to either the VR-condition or Care As Usual (CAU)-condition. Both groups received standard wound care and pain medication. The VR-group additionally received VR-distraction. The primary outcome measure was pain intensity (VAT 0-10). Secondary outcome measures were pain medication (Fentanyl spray and/or Piritramide) and satisfaction with WDC (VAT 0-10). Only 38 patients (VR-group: n = 21; CAU-group: n = 17) of the 128 intended patients were included during the study period due to several limitations (strict exclusion criteria and restrictions of the VR-equipment). No significant differences were found between both groups on pain intensity and medication. Both groups were also equally satisfied with WDC. Age showed a significant negative correlation with pain during WDC. In view of the small sample size, this study has restricted power and should be considered a pilot. Nevertheless, a RCT with between-subjects design across multiple WDCs was feasible and, given the speed of VR-developments, we expect larger, better powered RCTs to be possible in the near future, for which our experiences and recommendations are relevant.

Improvement of burn care by video interaction guidance.

AIMS: To evaluate the effect of video interaction guidance on improving the nurse-child relationship during the wound care procedures. Additionally, determine whether the interactional behavior of nurses is related to pain and distress experienced by children. METHODS: The interactional skills of seven nurses receiving video interaction guidance were compared with those of ten other nurses. The nurse-child interactions were video-taped during wound care procedures. Of the nurses receiving video interaction guidance, three wound dressing changes were videotaped before they received video interaction guidance and three after. The interaction between nurse and child was scored with the Nurse-child interaction taxonomy by two experienced raters. The COMFORT-B behavior scale was used to assess pain, and distress. All raters were blinded regarding video interaction guidance allocation and the sequence of tapes RESULTS: Five nurses in the intervention group (71 %) showed clinically relevant progress on the taxonomy while only four nurses (40 %) showed similar progress in the control group [p = .10]. A weak association was found between the nurses' interactions and the children's pain and distress [r = -.30, p = .002]. CONCLUSIONS: This is the first study to show that video interaction guidance can be used as a tool to train nurses to become more effective during patient encounters. Furthermore, nurses' interactional skills are positively associated with a child's pain and distress level.

Insights into the distribution and ingestion of prey-like plastic fishing lures in Mediterranean rough-toothed dolphins.

Rough-toothed dolphins (Steno bredanensis) form an isolated subpopulation in the Mediterranean Sea that resides only in the eastern basin. Due to the paucity of records, the conservation threats these dolphins face and their ecology and distribution are poorly understood. While most observations indicate that individuals are found in two isolated clusters in the eastern basin, we hereby present five observations -three visual, one acoustic and one stranding- that possibly extend the range of this subpopulation to the entire offshore waters of the eastern basin. The stomach content remains of the stranded individual revealed a diet based on epipelagic squids and octopods. The stranded dolphin had also consumed seven plastic bags and nine squid-like plastic fishing lures, which had caused a complete gastric blockage and probably led to the stranding. High pollution loads from macroplastics in the Mediterranean Sea may evolve into a new potential threat for this subpopulation.

Historical view of medical Spanish instruction in a medical school at the US-Mexico border region.

With a growing speaking Spanish population in the USA, it is necessary to help meet their healthcare needs. The Paul L. Foster School of Medicine is located in El Paso at the US-Mexico border. The medical Spanish curriculum is required for all medical students and begins on their first day of medical school, with conversational Spanish and medical Spanish through the preclerkship years. One of the key elements to the success of this course is the use of instructors with expertise in language instruction with an emphasis on task-based instruction. In addition to language instruction, this course also emphasizes instruction and experience in the culture of the US-Mexico border region. While taught medical Spanish, students are also prompted to understand when their skills are not adequate for the situation, in which case they need to enlist a skilled translator. Students report that, on a daily basis, they productively use what they learned in this preclerkship curriculum.

Health care professionals' perceptions of unprofessional behaviour in the clinical workplace.

BACKGROUND: Unprofessional behaviour undermines organizational trust and negatively affects patient safety, the clinical learning environment, and clinician well-being. Improving professionalism in healthcare organizations requires insight into the frequency, types, sources, and targets of unprofessional behaviour in order to refine organizational programs and strategies to prevent and address unprofessional behaviours. OBJECTIVE: To investigate the types and frequency of perceived unprofessional behaviours among health care professionals and to identify the sources and targets of these behaviours. METHODS: Data was collected from 2017-2019 based on a convenience sample survey administered to all participants at the start of a mandatory professionalism course for health care professionals including attending physicians, residents and advanced practice providers (APPs) working at one academic hospital in the United States. RESULTS: Out of the 388 participants in this study, 63% experienced unprofessional behaviour at least once a month, including failing to respond to calls/pages/requests (44.3%), exclusion from decision-making (43.0%) and blaming behaviour (39.9%). Other monthly experienced subtypes ranged from 31.7% for dismissive behaviour to 4.6% for sexual harassment. Residents were more than twice as likely (OR 2.25, p<0.001)) the targets of unprofessional behaviour compared to attending physicians. Female respondents experienced more discriminating behaviours (OR 2.52, p<0.01). Nurses were identified as the most common source of unprofessional behaviours (28.1%), followed by residents from other departments (21%). CONCLUSIONS: Unprofessional behaviour was experienced frequently by all groups, mostly inflicted on these groups by those outside of the own discipline or department. Residents were most frequently identified to be the target and nurses the source of the behaviours. This study highlights that unprofessional behaviour is varied, both regarding types of behaviours as well as targets and sources of such behaviours. This data is instrumental in developing training and remediation initiatives attuned to specific professional roles and specific types of professionalism lapses.

Intramuscular lipid utilization during exercise: a systematic review, meta-analysis, and meta-regression.

Intramuscular lipid (IMCL) utilization during exercise was controversial as numerous studies did not observe a decline in IMCL content post-exercise when assessed in muscle biopsies using biochemical techniques. Contemporary techniques including immunofluorescence microscopy and 1H-magnetic resonance spectroscopy (1H-MRS) offer advantages over biochemical techniques. The primary aim of this systematic review, meta-analysis, and meta-regression was to examine the net degradation of IMCL in response to an acute bout of cycling exercise in humans, as assessed with different analytical approaches. A secondary aim was to explore the factors influencing IMCL degradation including feeding status, exercise variables, and participant characteristics. A total of 44 studies met the inclusion criteria using biochemical, immunofluorescence, and 1H-MRS techniques. A meta-analysis was completed using a random effects model and percentage change in IMCL content calculated from the standardized mean difference. Cycling exercise resulted in a net degradation of IMCL regardless of technique (total effect -23.7%, 95% CI = -28.7 to -18.7%) and there was no difference when comparing fasted versus fed-state exercise (P > 0.05). IMCL degradation using immunofluorescence techniques detected larger effects in type I fibers compared with whole muscle using biochemical techniques (P = 0.003) and in type I fibers compared with type II fibers (P < 0.001). Although IMCL degradation was associated with exercise duration, V̇o2max, and BMI, none of these factors independently related to the change in IMCL content. These findings provide strong evidence that the analytical approach can influence the assessment of IMCL degradation in human skeletal muscle in response to exercise.

Detecting Changes in Tissue Perfusion With Hyperspectral Imaging and Thermal Imaging Following Endovascular Treatment for Peripheral Arterial Disease.

PURPOSE: Hyperspectral imaging (HSI) and thermal imaging allow contact-free tissue perfusion measurements and may help determine the effect of endovascular treatment (EVT) in patients with peripheral arterial disease. This study aimed to detect changes in perfusion with HSI and thermal imaging peri-procedurally and determine whether these changes can identify limbs that show clinical improvement after 6 weeks. METHODS: Patients with Rutherford class 2-6 scheduled for EVT were included prospectively. Hyperspectral imaging and thermal imaging were performed directly before and after EVT. Images were taken from the lateral side of the calves and plantar side of the feet. Concentrations of (de)oxyhemoglobin, oxygen saturation, and skin temperature were recorded. Angiographic results were determined on completion angiogram. Clinical improvement 6 weeks after EVT was defined as a decrease ≥ one Rutherford class. Peri-procedural changes in perfusion parameters were compared between limbs with and without good angiographic results or clinical improvement. To identify limbs with clinical improvement, receiver operating characteristic (ROC) curves were used to determine cutoff values for change in HSI. RESULTS: Included were 23 patients with 29 treated limbs. Change in HSI values and temperature was not significantly different between limbs with good and poor angiographic results. Change in peri-procedural deoxyhemoglobin, determined by HSI, at the calves and feet was significantly different between limbs with and without clinical improvement at 6 week follow-up (p=0.027 and p=0.017, respectively). The ROC curve for change in deoxyhemoglobin at the calves showed a cutoff value of ≤1.0, and ≤-0.5 at the feet, which were discriminative for clinical improvement (sensitivity 77%; specificity 75% and sensitivity 62%; specificity 88%, respectively). CONCLUSIONS: HSI can detect changes in perfusion at the calves after EVT in patients with Rutherford class 2-6. Peri-procedural deoxyhemoglobin changes at the calves and feet are significantly different between limbs with and without clinical improvement. Decrease in deoxyhemoglobin directly after EVT may identify limbs that show clinical improvement 6 weeks after EVT.

'Eye in the sky': Off-the-shelf unmanned aerial vehicle (UAV) highlights exposure of marine turtles to floating litter (FML) in nearshore waters of Mayo Bay, Philippines.

Litter is a serious threat to the marine environment, with detrimental effects on wildlife and marine biodiversity. Limited data as a result of funding and logistical challenges in developing countries hamper our understanding of the problem. Here, we employed commercial unmanned aerial vehicle (UAV) as a cost-effective tool to study the exposure of marine turtles to floating marine litter (FML) in waters of Mayo Bay, Philippines. A quadcopter UAV was flown autonomously with on-board camera capturing videos during the flight. Still frames were extracted when either turtle or litter were detected in post-flight processing. The extracted frames were georeferenced and mapped using QGIS software. Results showed that turtles are highly exposed to FML in nearshore waters. Moreover, spatial dependence between FML and turtles was also observed. The study highlights the effectiveness of UAVs in marine litter research and underscores the threat of FML to turtles in nearshore waters.

Incomplete bunyavirus particles can cooperatively support virus infection and spread.

Bunyaviruses lack a specific mechanism to ensure the incorporation of a complete set of genome segments into each virion, explaining the generation of incomplete virus particles lacking one or more genome segments. Such incomplete virus particles, which may represent the majority of particles produced, are generally considered to interfere with virus infection and spread. Using the three-segmented arthropod-borne Rift Valley fever virus as a model bunyavirus, we here show that two distinct incomplete virus particle populations unable to spread autonomously are able to efficiently complement each other in both mammalian and insect cells following co-infection. We further show that complementing incomplete virus particles can co-infect mosquitoes, resulting in the reconstitution of infectious virus that is able to disseminate to the mosquito salivary glands. Computational models of infection dynamics predict that incomplete virus particles can positively impact virus spread over a wide range of conditions, with the strongest effect at intermediate multiplicities of infection. Our findings suggest that incomplete particles may play a significant role in within-host spread and between-host transmission, reminiscent of the infection cycle of multipartite viruses.

Determination of Changes in Tissue Perfusion at Home with Hyperspectral and Thermal Imaging in the First Six Weeks after Endovascular Therapy in Patients with Peripheral Arterial Disease.

The aims of this study were to assess changes in tissue perfusion up to 6 weeks after endovascular therapy (EVT), in hospital and at home, and to determine differences in tissue perfusion between patients with and without clinical improvement or good angiographic result. This single-center prospective cohort study included patients undergoing EVT for Rutherford stages two to six. Hyperspectral and thermal imaging were performed at the dorsal and plantar sides of the foot. These measurements consisted of a baseline measurement pre-EVT, and six follow-up measurements obtained at 1 and 4 h and 6 weeks in hospital, and 1 day, 7 days, and 14 days at home. Clinical improvement was defined as a decrease of one or more Rutherford class or decrease in the wound surface area and a good angiographic result was accomplished when a Transatlantic Inter-Society Consensus for the Management of PAD II C or D lesion was treated and uninterrupted flow continued in at least one below-the-knee artery in continuation with the inframalleolar arteries. The study included 34 patients with 41 treated limbs. Deoxyhemoglobin values were lower 1 h post-EVT compared with baseline and increased over time up to 6 weeks post-EVT. Significant differences in deoxyhemoglobin levels at 7 and 14 days post-EVT were determined between patients with and without clinical or angiographic success. This prospective pilot study shows the feasibility of hyperspectral imaging and thermal imaging post-EVT at home, which may decrease the need for hospital visits.

Global Health 101.

Global health is an evolving field that has been broadly defined as the promotion of health for all through transnational collaboration and research. It centers on the concepts of equity and collaboration. The focus of global health has recently undergone a major shift toward emphasizing the importance of a systems-based approach to healthcare delivery, which considers not only the target disease but also the many contextual factors, influencing the ability to deliver care equitably to a population to reduce the burden of any particular disease. Thus, an important global health delivery framework has been established to outline this inter- and multi-disciplinary systems-based to address major global health issues and improve health for all globally. The practice of global health, whether in research or in active intervention, necessitates guiding principles to ensure ethical conduct in the transnational partnerships and efforts to advance the field. With the introduction of the United Nations' Sustainable Development Goals in 2015, there has been a major shift in response to epidemiologic transition to focus on reducing the burden of noncommunicable diseases, including cancer, which disproportionately impact low-to-middle income countries. This is true for colorectal cancer, with care challenged by significant gaps in screening, early detection, and referral systems.