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The United States has the highest maternal mortality rate among developed countries, with cardiovascular disease (CVD) being one of the leading causes of maternal deaths. Diagnosing CVD during pregnancy may be challenging as symptoms of normal pregnancy overlap with those of CVD. Delays in recognition and response to the diagnosis of CVD is a missed opportunity for timely intervention to improve maternal outcomes. Implementing universal CVD risk assessment for all pregnant and postpartum patients across clinical care settings presents a pivotal opportunity to address this issue. Integrating a validated risk assessment tool into routine obstetric care, clinicians, including obstetricians, primary care, and emergency healthcare providers, can enhance awareness of cardiovascular risk and facilitate early CVD diagnosis. Consensus among stakeholders underscores the importance of screening and education on cardiovascular health strategies for pregnant and postpartum patients to reduce CVD-related maternal mortality. This comprehensive approach offers a pathway to identify at-risk individuals and intervene promptly, potentially saving lives and advancing maternal healthcare equity.

BACKGROUND: Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry-based cohort, we documented prevalence of lifetime and past-month SCAD-induced PTSD, as well as related treatment seeking, and examined a range of health-relevant correlates of SCAD-induced PTSD. METHODS AND RESULTS: Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD-induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD-induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD-induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past-month PTSD. Of 811 patients ever reporting any SCAD-induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD-induced PTSD diagnoses reported never receiving trauma-related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past-month PTSD symptom severity in multivariable regression models. Greater past-month SCAD-induced PTSD symptoms were associated with greater past-week sleep disturbance and worse past-month disease-specific health status when adjusting for various risk factors. CONCLUSIONS: Given the high prevalence of SCAD-induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.

Despite marked advancements in the recognition and diagnosis of spontaneous coronary artery dissection (SCAD) over the past decade, knowledge of the basic pathophysiologic mechanisms of disease, contributing factors, and treatment continue to be poorly understood. We describe significant research gaps in our knowledge of SCAD and introduce strategies including the role of patient advocacy, independent registries, and creation of diverse centers of excellence to bridge the gap in clinical care, research, and outcomes. Lastly, we introduce an innovative patient-centered clinical care and research framework established through the SCAD Alliance and International Spontaneous Coronary Artery Dissection registry as a model for advancing knowledge of SCAD.

The United States has the highest maternal mortality rate among developed countries, with cardiovascular disease (CVD) being one of the leading causes of maternal deaths. Diagnosing CVD during pregnancy may be challenging as symptoms of normal pregnancy overlap with those of CVD. Delays in recognition and response to the diagnosis of CVD is a missed opportunity for timely intervention to improve maternal outcomes. Implementing universal CVD risk assessment for all pregnant and postpartum patients across clinical care settings presents a pivotal opportunity to address this issue. Integrating a validated risk assessment tool into routine obstetric care, clinicians, including obstetricians, primary care, and emergency healthcare providers, can enhance awareness of cardiovascular risk and facilitate early CVD diagnosis. Consensus among stakeholders underscores the importance of screening and education on cardiovascular health strategies for pregnant and postpartum patients to reduce CVD-related maternal mortality. This comprehensive approach offers a pathway to identify at-risk individuals and intervene promptly, potentially saving lives and advancing maternal healthcare equity.

Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage-synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies.

Background Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry‐based cohort, we documented prevalence of lifetime and past‐month SCAD‐induced PTSD, as well as related treatment seeking, and examined a range of health‐relevant correlates of SCAD‐induced PTSD. Methods and Results Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD‐induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD‐induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD‐induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past‐month PTSD. Of 811 patients ever reporting any SCAD‐induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD‐induced PTSD diagnoses reported never receiving trauma‐related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past‐month PTSD symptom severity in multivariable regression models. Greater past‐month SCAD‐induced PTSD symptoms were associated with greater past‐week sleep disturbance and worse past‐month disease‐specific health status when adjusting for various risk factors. Conclusions Given the high prevalence of SCAD‐induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.

Abstract Aims To investigate the diagnostic accuracy of fecal calprotectin (FC) for inflammatory bowel disease (IBD) and organic gastrointestinal disease (OGID) in primary care. To examine the association with demographic factors, symptoms and concomitant medical therapy. Methods A retrospective analysis of data on all semiquantitative FC tests from individuals ≥18 years conducted in primary care in Östergötland County in 2010. A 5‐year follow‐up with inclusion of new gastrointestinal diagnoses. Results A total of 1293 eligible patients were included. IBD was found in 8.8% and other OGID in 30.8% of patients with positive FC. Positive FC was associated with diarrhea, age >60 years, duration 35 years, abnormal clinical findings, and duration 35 years, should encourage a prioritized investigation. Use of NSAID, PPI, and ASA may affect the diagnostic accuracy of FC for IBD and OGID.

In this paper, we undertake a critical analysis of how chatbots built on generative artificial intelligence impact assumptions underlying definitions of trust. We engage a particular definition of trust and the object-oriented model of trust that was built upon it and identify how at least four implicit assumptions may no longer hold. Those assumptions include that people generally provide others with a default level of trust, the ability to identify whether the trusted agent is human or artificial, that risk and trust can be readily quantified or categorized, and that there is no expectation of gain by agents engaged in trust relationships. Based on that analysis, we suggest modifications to the definition and model to accommodate the features of generative AI chatbots. Our changes re-emphasize developers’ responsibility for the impacts of their AI artifacts, no matter how sophisticated the artifact may be. The changes also reflect that trust relationships are more fraught when participants in such relationships are not confident in identifying the nature of a potential trust partner.

Abstract Background In order to improve detection of suspected infections in frail elderly there is an urgent need for development of decision support tools, that can be used in the daily work of all healthcare professionals for assessing non-specific and specific changes. The aim was to study non-specific signs and symptoms and fever temperature for early detection of ongoing infection in frail elderly, and how these correlates to provide the instrument, the Early Detection Infection Scale (EDIS), which is used to assess changes in health condition in frail elderly. Methods This was an explorative, prospective cohort study, including 45 nursing home residents, 76 to 99 years, in Sweden. Nursing assistants measured morning ear body temperature twice a week and used the EDIS to assess individual health condition daily for six months. The outcome comprised events of suspected infection, compiled from nursing and medical patient records. Factor analysis and multivariate logistic regression analysis were performed to analyse data. Results Fifteen residents were diagnosed with at least one infection during the six-month follow-up and 189 observations related to 72 events of suspected infection were recorded. The first factor analysis revealed that the components, change in cognitive and physical function, general signs and symptoms of illness, increased tenderness, change in eye expression and food intake and change in emotions explained 61% of the variance. The second factor analysis, adding temperature assessed as fever to > 1.0 °C from individual normal, resulted in change in physical function and food intake, confusion and signs and symptoms from respiratory and urinary tract, general signs and symptoms of illness and fever and increased tenderness, explaining 59% of the variance. In the first regression analysis, increased tenderness and change in eye expression and food intake, and in the second change in physical function and food intake, general signs and symptoms of illness and fever (> 1.0 °C from individual normal) and increased tenderness were significantly associated with increased risk for ongoing infection. Conclusion No items in the EDIS should be removed at present, and assessment of fever as > 1.0 °C from individual normal is a valuable addition. The EDIS has the potential to make it easier for first line caregivers to systematically assess changes in health condition in fragile elderly people and helps observations to be communicated in a standardised way throughout the care process. The EDIS thus contributes to ensuring that the decisions not being taken at the wrong level of care.

Abstract Background In many biological and therapeutic contexts, it is highly desirable to target a chemical specifically to a particular tissue where it exerts its biological effect. In this paper, we present a simple, generic, mathematical model that elucidates a general method for targeting a chemical to particular tissues. The model consists of coupled reaction-diffusion equations to describe the evolution within the tissue of the concentrations of three chemical species: a (concentration of free chemical), b (binding protein) and their complex, c (chemical bound to binding protein). We assume that all species are free to diffuse, and that a and b undergo a reversible reaction to form c. In addition, the complex, c, can be broken down by a process (e.g. an enzyme in the tissue) that results in the release of the chemical, a, which is then free to exert its biological action. Results For simplicity, we consider a one-dimensional geometry. In the special case where the rate of complex formation is small (compared to the diffusion timescale of the species within the tissue) the system can be solved analytically. This analytic solution allows us to show how the concentration of free chemical, a, in the tissue can be increased over the concentration of free chemical at the tissue boundary. We show that, under certain conditions, the maximum concentration of a can occur at the centre of the tissue, and give an upper bound on this maximum level. Numerical simulations are then used to determine how the behaviour of the system changes when the assumption of negligible complex formation rate is relaxed. Conclusions We have shown, using our mathematical model, how complex degradation can potentially be exploited to target a chemical to a particular tissue, and how the level of the active chemical depends on factors such as the diffusion coefficients and degradation/production rates of each species. The biological significance of these results in terms of potential applications in cartilage tissue engineering and chemotherapy is discussed. In particular, we believe these results may be of use in determining the most promising prodrug candidates.

Negated sentences are known to be more cognitively taxing than positive ones (i.e., "polarity effect"). We present evidence that two factors contribute to the polarity effect in verification tasks: processing the sentence and verifying its truth value. To quantify the relative contribution of each, we used a delayed verification task. The results show that even when participants are given a considerable amount of time for processing the sentence prior to verification, the polarity effect is not entirely eliminated. We suggest that this sustained effect stems from a retained negation-containing representation in working memory.

Zhang et al. show that the Creb5 transcription factor regulates the formation of synovial joints, directs the genesis of articular cartilage, and regulates the shape of the ends of long bones by blocking Wnt5a expression in the perichondrium.

Abstract Background Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease. Methods Osteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin’s grade 0–2, 23–83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile. Results Immediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified. Conclusion CBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression.

Abstract Background Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo human osteochondral model of PTOA to investigate disease effects on cartilage and bone homeostasis and discover biomarkers for disease progression and drug efficacy. Methods Human osteochondral explants were harvested from normal (Collins grade 0–1) ankle talocrural joints of human donors (2 female, 5 male, ages 23–70). After pre-equilibration, osteochondral explants were treated with a single-impact mechanical injury and TNF-α, IL-6, and sIL-6R ± 100 nM Dex for 21 days and media collected every 2–3 days. Chondrocyte viability, tissue DNA content, and glycosaminoglycan (sGAG) percent loss to the media were assayed and compared to untreated controls using a linear mixed effects model. Mass spectrometry analysis was performed for both cartilage tissue and pooled culture medium, and the statistical significance of protein abundance changes was determined with the R package limma and empirical Bayes statistics. Partial least squares regression analyses of sGAG loss and Dex attenuation of sGAG loss against proteomic data were performed. Results Injury and cytokine treatment caused an increase in the release of matrix components, proteases, pro-inflammatory factors, and intracellular proteins, while tissue lost intracellular metabolic proteins, which was mitigated with the addition of Dex. Dex maintained chondrocyte viability and reduced sGAG loss caused by injury and cytokine treatment by 2/3 overall, with donor-specific differences in the sGAG attenuation effect. Biomarkers of bone metabolism had mixed effects, and collagen II synthesis was suppressed with both disease and Dex treatment by 2- to 5-fold. Semitryptic peptides associated with increased sGAG loss were identified. Pro-inflammatory humoral proteins and apolipoproteins were associated with lower Dex responses. Conclusions Catabolic effects on cartilage tissue caused by injury and cytokine treatment were reduced with the addition of Dex in this osteochondral PTOA model. This study presents potential peptide biomarkers of early PTOA progression and Dex efficacy that can help identify and treat patients at risk of PTOA.

Background/Objectives: Individual habitual conditions entail a risk during the interpretation of vital parameters. We developed algorithms for calculating, validating, and interpreting individual normal ranges of body temperature and oxygen saturation. Methods: In total, 70 healthy individuals aged 27 to 80 and 52 frail individuals aged 60 to 100 were included. Data on individual conditions comprised age, gender, physical ability, chronic disease, and medication. Ear temperature and oxygen saturation were measured for five mornings before the participants got out of bed and consumed medicine, food, or drink. Results: The range for body temperature was 34.3 °C to 37.7 °C, with a variation of 0.7 °C ± 0.4 °C. The variation in minimum and maximum temperatures was 2.4 °C vs. 2.7 °C and 2.9 °C vs. 2.3 °C in healthy and frail subjects, respectively. The range for oxygen saturation was 85% to 99% in healthy individuals and 75% to 100% in frail individuals. The variation between minimum and maximum oxygen saturation was 13% vs. 25% and 4% vs. 17% in healthy and frail subjects, respectively. Conclusions: To promote the implementation of precision medicine in clinical practice, it is necessary to interpret body temperature and oxygen saturation based on individual habitual conditions. Interpreting deviations from an individual's normal ranges allows healthcare professionals to provide necessary treatment without delay, which can be decisive in preventing further deterioration. [ABSTRACT FROM AUTHOR]

The study uses data from state and industry official statistics for 2008-2017. Absolute and relative indicators of morbidity and prevalence of chronic cystitis among the female population of Ukraine, its regions and areas were analyzed taking into account two five-year periods for comparative assessment of the nature and intensity of dynamic processes. It is revealed that the number of patients with chronic cystitis (СC) registered in Ukraine is at the expense of women, which are 3-3.5 times more in number than men, with their characteristic more intensive growth (for 10 years by 3.6% against 0.4% among the adult population in the country). The first three places in the structure belong to the Southeastern region, Kyiv, Western region, the next – Central, Southern, Northeastern regions. Levels of the prevalence of the disease among women (100 thousand) are higher than the average in Ukraine and have a high growth rate (for 10 years by 13.5% from 232.2 to 263.6 against 9.3% from 171.5 to 187.5, respectively). Typical for Ukraine persistent increase in patients with the first diagnosis of chronic cystitis (0.8%, 2.1% and 2.8%, respectively, in the first, second periods and 10 years to 15112 in 2017) is also formed by this category (women's growth was 3.4%, 12.4%, and 5.0%, respectively, to 11.295). A similar situation was also identified in the analysis of the level of morbidity (per 100 thousand). In Ukraine, its growth rate for the last five years was 9.6% against 1.8% for the previous year, for 10 years – 11.9%, and the value reached 43.4 in 2017 against 38.8 in 2008. Among women, its levels are higher than the average in Ukraine (in 2017 – 59.2 against 56.1 in 2008), and the increase was more intense (by 6.2% and 11.3% over the periods; for 10 years – by 11.98%).