Painful Subjects, Desiring Relief: Experiencing and Governing Pain in a Medical Cannabis Program.

Cannabis can provide patients benefits for pain and symptom management, improve their functionality, and enhance their well-being. Yet restrictive medical cannabis programs can limit these potential benefits. This article draws on four years of research into Minnesota's medical cannabis program-one of the most restrictive in the United States-including in-depth interviews with patients and a survey of health care professionals. Drawing on the new materialist concepts of Deleuze and Guattari, this article analyzes (a) the benefits patients in Minnesota's medical cannabis program derive from cannabis, (b) how program restrictions mediate access to cannabis and its derived benefits, and (c) some key ways in which medical and criminal justice institutional authorities are reconfigured around medical cannabis. I show how the imperative to authoritatively govern "dangerous drugs" persists in consequential ways as the War on Drugs shifts toward a medicalized, criminalized, and commercial-legalized mixed regime.

Adoption of Reverse Total Shoulder Arthroplasty for Surgical Treatment of Proximal Humerus Fractures Differs by Patient Race.

BACKGROUND: Reverse total shoulder arthroplasty (rTSA) has gained popularity for the operative treatment of proximal humerus fractures (PHF). The purpose of this study was to compare racial differences in surgical management of PHF between open reduction and internal fixation (ORIF), hemiarthroplasty, and rTSA. Our hypothesis was that there would be no difference in fixation by race. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for ORIF, rTSA, and hemiarthroplasty between 2006 and 2020 for patients with a PHF. Race, ethnicity, age, sex, body mass index (BMI), and American Society of Anesthesiologists (ASA) class were recorded. Chi squared tests were performed to assess relationships between patient factors and operative intervention. Factors significant at the 0.10 level in univariable analyses were included in a multivariable multinomial model to predict operative intervention. RESULTS: 7,499 patients underwent surgical treatment for a PHF, including 526 (7%) undergoing hemiarthroplasty, 5,011 (67%) undergoing ORIF, and 1,962 (26%) undergoing rTSA. 27% of white patients with PHF underwent rTSA compared to 21% of Black patients, 16% of Asian patients, and 14% of Native American and Alaskan Native patients (p<0.001). In the multivariable analysis, utilization of rTSA increased over time (OR 1.2 per year since 2006, p < 0.001) and hemiarthroplasty decreased over time (OR 0.86 per year since 2006, p < 0.001). Non-white patients had significantly lower odds of undergoing rTSA versus ORIF (OR 0.75, 95% CI 0.58-0.97), as did male patients (OR 0.77, 95% CI 0.66-0.88). Patients over 65 (OR 3.86, 95% CI 3.39-4.38), patients with higher ASA classifications (ASA2: OR 3.24, 95% CI 1.86-5.66, ASA3: OR 4.77, 95% CI 2.74-8.32, ASA4: OR 5.25, 95% CI 2.89-9.54), and patients who were overweight (OR 1.33, 95% CI 1.14-1.55) or obese (OR 1.52, 95% CI 1.32-1.75) had higher odds of undergoing rTSA versus ORIF. DISCUSSION: As utilization of rTSA increases, understanding disparities in surgical treatment of PHF is crucial to improving outcomes and equitable access to emerging orthopedic technologies. While patient factors such as age, BMI, and comorbidities are known to directly impact outcomes and thus may be predictive of the type of surgical intervention, patient race should not dictate treatment.

Dapagliflozin Enhances Arterial and Venous Compliance During Exercise in Heart Failure With Preserved Ejection Fraction: Insights From the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial.

BACKGROUND: Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. METHODS: In this secondary analysis from the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial, 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. RESULTS: There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). CONCLUSIONS: In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

Patient-specific quality assurance of dynamically-collimated proton therapy treatment plans.

BACKGROUND: The dynamic collimation system (DCS) provides energy layer-specific collimation for pencil beam scanning (PBS) proton therapy using two pairs of orthogonal nickel trimmer blades. While excellent measurement-to-calculation agreement has been demonstrated for simple cube-shaped DCS-trimmed dose distributions, no comparison of measurement and dose calculation has been made for patient-specific treatment plans. PURPOSE: To validate a patient-specific quality assurance (PSQA) process for DCS-trimmed PBS treatment plans and evaluate the agreement between measured and calculated dose distributions. METHODS: Three intracranial patient cases were considered. Standard uncollimated PBS and DCS-collimated treatment plans were generated for each patient using the Astroid treatment planning system (TPS). Plans were recalculated in a water phantom and delivered at the Miami Cancer Institute (MCI) using an Ion Beam Applications (IBA) dedicated nozzle system and prototype DCS. Planar dose measurements were acquired at two depths within low-gradient regions of the target volume using an IBA MatriXX ion chamber array. RESULTS: Measured and calculated dose distributions were compared using 2D gamma analysis with 3%/3 mm criteria and low dose threshold of 10% of the maximum dose. Median gamma pass rates across all plans and measurement depths were 99.0% (PBS) and 98.3% (DCS), with a minimum gamma pass rate of 88.5% (PBS) and 91.2% (DCS). CONCLUSIONS: The PSQA process has been validated and experimentally verified for DCS-collimated PBS. Dosimetric agreement between the measured and calculated doses was demonstrated to be similar for DCS-collimated PBS to that achievable with noncollimated PBS.

The benefits of socioemotional learning strategies and video formats for older digital immigrants learning a novel smartphone application.

The need to continually learn and adjust to new technology can be an arduous demand, particularly for older adults who did not grow up with digital technology ("older digital immigrants" or ODIs). This study tests the efficacy of socioemotional learning strategies (i.e., encoding information in a socially- or emotionally-meaningful way) for ODIs learning a new software application from an instructional video (Experiment 1) or a written manual (Experiment 2). An experiment-by-condition effect was identified, where memory was greatest for participants engaging socioemotional learning strategies while learning from a video, suggesting a synergistic effect of these manipulations. These findings serve as a first step toward identifying and implementing an optimal learning context for ODIs to learn new technologies in everyday life.

Direct Numerical Solutions to Stochastic Differential Equations with Multiplicative Noise.

Inspired by path integral solutions to the quantum relaxation problem, we develop a numerical method to solve classical stochastic differential equations with multiplicative noise that avoids averaging over trajectories. To test the method, we simulate the dynamics of a classical oscillator multiplicatively coupled to non-Markovian noise. When accelerated using tensor factorization techniques, it accurately estimates the transition into the bifurcation regime of the oscillator and outperforms trajectory-averaging simulations with a computational cost that is orders of magnitude lower.

Writing Groups for Healthcare Professionals in Academic Medicine.

Within the Department of Medicine (DOM) in a large tertiary academic health care facility in midwestern United States, we have developed an educational offering that incorporates an academic writing program (AWP) blending the approaches of a writing accountability work group, a writing workshop, and didactic writing courses. The purpose of this AWP was to assist healthcare professionals (HCP) with their manuscript writing skills to enhance academic productivity. We report our evolving journey and experiences with this AWP. To date, it has been offered 3 times to 25 HCP over the course of 3 years. Among those responding to a post program follow up survey (N = 11), 8 (73%) indicated that they completed the project that they were working on during the AWP and went on to publish the manuscript (N = 5) or were in the process of submission (N = 2). Some indicated they has also gone on to present posters (N = 2) or were in the process of presenting posters (N = 2) or had received grants (N = 1) or were awaiting grant notice (N = 1). A number of attendees have continued to use and share the tools presented during the AWP. Based on input from attendees and increased requests for this AWP, this educational program has been deemed a success and expansion of this program is currently underway.

Image-guided patient-specific optimization of catheter placement for convection-enhanced nanoparticle delivery in recurrent glioblastoma.

BACKGROUND: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (186Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM). METHODS: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient (CCC) was used to quantify the agreement between the predicted and measured SPECT signals. The model was then used to simulate RNL distributions from a range of catheter placements, resulting in a ratio of the cumulative RNL dose outside versus inside the tumor, the "off-target ratio" (OTR). Optimal catheter placement) was identified by minimizing OTR. RESULTS: Fifteen patients with rGBM from a Phase I/II clinical trial (NCT01906385) were recruited to the study. Our model, with either individual-calibrated or population-assigned parameters, achieved high accuracy (CCC > 0.80) for predicting RNL distributions up to 24 h after delivery. The optimal catheter placements identified using this model achieved a median (range) of 34.56 % (14.70 %-61.12 %) reduction on OTR at the 24 h post-delivery in comparison to the original placements. CONCLUSIONS: Our image-guided model achieved high accuracy for predicting patient-specific RNL distributions and indicates value for optimizing catheter placement for CED of radiolabeled liposomes.

Predicting Recovery Following Total Hip and Knee Arthroplasty Using a Clustering Algorithm.

Background: Recovery following total joint arthroplasty is patient-specific, yet groups of patients tend to fall into certain similar patterns of recovery. The purpose of this study was to identify and characterize recovery patterns following total hip arthroplasty (THA) and total knee arthroplasty (TKA) using patient-reported outcomes that represent distinct health domains. We hypothesized that recovery patterns could be defined and predicted using preoperative data. Methods: Adult patients were recruited from a large, urban academic center. To model postoperative responses to THA and TKA across domains such as physical health, mental health, and joint-specific measures, we employed a longitudinal clustering algorithm that incorporates each of these health domains. The clustering algorithm from multiple health domains allows the ability to define distinct recovery trajectories, which could then be predicted from preoperative and perioperative factors using a multinomial regression. Results: Four hundred forty-one of 1134 patients undergoing THA and 346 of 921 undergoing TKA met eligibility criteria and were used to define distinct patterns of recovery. The clustering algorithm was optimized for 3 distinct patterns of recovery that were observed in THA and TKA patients. Patients recovering from THA were divided into 3 groups: standard responders (50.8%), late mental responders (13.2%), and substandard responders (36.1%). Multivariable, multinomial regression suggested that these 3 groups had defined characteristics. Late mental responders tended to be obese (P = .05) and use more opioids (P = .01). Substandard responders had a larger number of comorbidities (P = .02) and used more opioids (P = .001). Patients recovering from TKA were divided among standard responders (55.8%), poor mental responders (24%), and poor physical responders (20.2%). Poor mental responders were more likely to be female (P = .04) and American Society of Anesthesiologists class III/IV (P = .004). Poor physical responders were more likely to be female (P = .03), younger (P = .04), American Society of Anesthesiologists III/IV (P = .04), use more opioids (P = .02), and be discharged to a nursing facility (P = .001). The THA and TKA models demonstrated areas under the curve of 0.67 and 0.72. Conclusions: This multidomain, longitudinal clustering analysis defines 3 distinct patterns in the recovery of THA and TKA patients, with most patients in both cohorts experiencing robust improvement, while others had equally well defined yet less optimal recovery trajectories that were either delayed in recovery or failed to achieve a desired outcome. Patients in the delayed recovery and poor outcome groups were slightly different between THA and TKA. These groups of patients with similar recovery patterns were defined by patient characteristics that include potentially modifiable comorbid factors. This research suggests that there are multiple defined recovery trajectories after THA and TKA, which provides a new perspective on THA and TKA recovery. Level of Evidence: III.

Understanding the Effects of Anode Catalyst Conductivity and Loading on Catalyst Layer Utilization and Performance for Anion Exchange Membrane Water Electrolysis.

Anion exchange membrane water electrolysis (AEMWE) is a promising technology to produce hydrogen from low-cost, renewable power sources. Recently, the efficiency and durability of AEMWE have improved significantly due to advances in the anion exchange polymers and catalysts. To achieve performances and lifetimes competitive with proton exchange membrane or liquid alkaline electrolyzers, however, improvements in the integration of materials into the membrane electrode assembly (MEA) are needed. In particular, the integration of the oxygen evolution reaction (OER) catalyst, ionomer, and transport layer in the anode catalyst layer has significant impacts on catalyst utilization and voltage losses due to the transport of gases, hydroxide ions, and electrons within the anode. This study investigates the effects of the properties of the OER catalyst and the catalyst layer morphology on performance. Using cross-sectional electron microscopy and in-plane conductivity measurements for four PGM-free catalysts, we determine the catalyst layer thickness, uniformity, and electronic conductivity and further use a transmission line model to relate these properties to the catalyst layer resistance and utilization. We find that increased loading is beneficial for catalysts with high electronic conductivity and uniform catalyst layers, resulting in up to 55% increase in current density at 2 V due to decreased kinetic and catalyst layer resistance losses, while for catalysts with lower conductivity and/or less uniform catalyst layers, there is minimal impact. This work provides important insights into the role of catalyst layer properties beyond intrinsic catalyst activity in AEMWE performance.

Kidney Function Assessment Using Cystatin C and Serum Creatinine in Heart Transplantation Recipients: Implications for Valganciclovir Dosing.

BACKGROUND: Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in extrarenal variables (e.g., muscle mass). Cystatin C (cysC) is less influenced by muscle mass; however, obesity and steroid use may increase cysC levels. Herein, we: i) longitudinally compared changes in eGFRcysC and eGFRsCr among HT recipients; ii) investigated the association of body mass index (BMI), steroid use and muscle mass with discrepancies between eGFRs; and iii) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing. METHODS: cysC and sCr were measured in 294 blood samples obtained from 80 HT recipients. Intra-individual differences between eGFRs (eGFRdiffcysC-sCr) were calculated. Negative eGFRdiffcysC-sCr values correspond to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n=21), pectoralis muscle measures were derived from computed tomography scans. RESULTS: Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr -28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient post-operative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Conversely, pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction. CONCLUSIONS: Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.

A Near-Infrared-II Excitable Pyridinium Probe with 1000-Fold ON/OFF Ratio for γ-Glutamyltranspeptidase and Cancer Detection.

Activity-based detection of γ-Glutamyltranspeptidase (GGT) using near-infrared (NIR) fluorescent probes is a promising strategy for early cancer diagnosis. Although NIR pyridinium probes show high performance in biochemical analysis, the aggregation of both the probes and parental fluorochromes in biological environments is prone to result in a low signal-to-noise ratio (SBR), thus affecting their clinical applications. Here, we develop a GGT-activatable aggregate probe called OTBP-G for two-photon fluorescence imaging in various biological environments under 1040 nm excitation. By rationally tunning the hydrophilicity and donor-acceptor strength, we enable a synergistic effect between twisted intramolecular charge transfer and intersystem crossing processes and realize a perfect dark state for OTBP-G before activation. After the enzymatic reaction, the parental fluorochrome exhibits bright aggregation-induced emission peaking at 670 nm. The fluorochrome-to-probe transformation can induce 1000-fold fluorescence ON/OFF ratio, realizing in vitro GGT detection with an SBR > 900. Activation of OTBP-G occurs within 1 min in vivo, showing an SBR > 400 in mouse ear blood vessels. OTBP-G can further enable the early detection of pulmonary metastasis in breast cancer by topically spraying, outperforming the clinical standard hematoxylin and eosin staining. We anticipate that the in-depth study of OTBP-G can prompt the development of early cancer diagnosis and tumor-related physiological research. Moreover, this work highlights the crucial role of hydrophilicity and donor-acceptor strength in maximizing the ON/OFF ratio of the TICT probes and showcases the potential of OTBP as a versatile platform for activity-based sensing.

Understanding mechanisms of generalization following locomotor adaptation.

Our nervous system has the remarkable ability to adapt our gait to accommodate changes in our body or surroundings. However, our adapted walking patterns often generalize only partially (or not at all) between different contexts. Here, we sought to understand how the nervous system generalizes adapted gait patterns from one context to another. Through a series of split-belt treadmill walking experiments, we evaluated different mechanistic hypotheses to explain the partial generalization of adapted gait patterns from split-belt treadmill to overground walking. In support of the credit assignment hypothesis, our experiments revealed the central finding that adaptation involves recalibration of two distinct forward models. Recalibration of the first model generalizes to overground walking, suggesting that the model represents the general movement dynamics of our body. On the other hand, recalibration of the second model does not generalize to overground walking, suggesting the model represents dynamics specific to treadmill walking. These findings reveal that there is a predefined portion of forward model recalibration that generalizes across context, leading to overall partial generalization of walking adaptation.

Late-Stage C(sp2)-C(sp3) Diversification via Nickel Oxidative Addition Complexes.

Herein, we describe nickel oxidative addition complexes (Ni-OACs) of drug-like molecules as a platform to rapidly generate lead candidates with enhanced C(sp3) fraction. The potential of Ni-OACs to access new chemical space has been assessed not only in C(sp2)-C(sp3) couplings but also in additional bond formations without recourse to specialized ligands and with improved generality when compared to Ni-catalyzed reactions. The development of an automated diversification process further illustrates the robustness of Ni-OACs, thus offering a new gateway to expedite the design-make-test-analyze (DMTA) cycle in drug discovery.

Case-control study on post-COVID-19 conditions reveals severe acute infection and chronic pulmonary disease as potential risk factors.

Post-COVID-19 conditions (long COVID) has impacted many individuals, yet risk factors for this condition are poorly understood. This retrospective analysis of 88,943 COVID-19 patients at a multi-state US health system compares phenotypes, laboratory tests, medication orders, and outcomes for 1,086 long-COVID patients and their matched controls. We found that history of chronic pulmonary disease (CPD) (odds ratio: 1.9, 95% CI: [1.5, 2.6]), migraine (OR: 2.2, [1.6, 3.1]), and fibromyalgia (OR: 2.3, [1.3, 3.8]) were more common for long-COVID patients. During the acute infection phase long COVID patients exhibited high triglycerides, low HDL cholesterol, and a high neutrophil-lymphocyte ratio; and were more likely hospitalized (5% vs. 1%). Our findings suggest severity of acute infection and history of CPD, migraine, chronic fatigue syndrome (CFS), or fibromyalgia as risk factors for long COVID. These results suggest that suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.

Immediate myeloid depot for SARS-CoV-2 in the human lung.

In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in the distal lung expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent, and therefore, the model of viral expansion and immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2 allowing both spike-ACE2-dependent viral entry and infection. In contrast to Influenza A virus, SARS-CoV-2 infection of AMs was productive, amplifying viral titers. While AMs generated new viruses, the interferon responses to SARS-CoV-2 were muted, hiding the viral dissemination from specific antiviral immune responses. The reliable and veiled viral depot in myeloid cells in the very early phases of SARS-CoV-2 infection of human lungs enables viral expansion in the distal lung and potentially licenses subsequent immune pathologies.

Assessing current and future available resources to supply urban water demands using a high-resolution SWAT model coupled with recurrent neural networks and validated through the SIMPA model in karstic Mediterranean environments.

Hydrological simulation in karstic areas is a hard task due to the intrinsic intricacy of these environments and the common lack of data related to their geometry. Hydrological dynamics of karstic sites in Mediterranean semiarid regions are difficult to be modelled mathematically owing to the existence of short wet episodes and long dry periods. In this paper, the suitability of an open-source SWAT method was checked to estimate the comportment of a karstic catchment in a Mediterranean semiarid domain (southeast of Spain), which wet and dry periods were evaluated using box-whisker plots and self-developed wavelet test. A novel expression of the Nash-Sutcliffe index for arid areas (ANSE) was considered through the calibration and validation of SWAT. Both steps were completed with 20- and 10-year discharge records of stream (1996-2015 to calibrate the model as this period depicts minimum gaps and 1985-1995 to validate it). Further, SWAT assessments were made with records of groundwater discharge and relating SWAT outputs with the SIMPA method, the Spain's national hydrological tool. These methods, along with recurrent neural network algorithms, were utilised to examine current and predicted water resources available to supply urban demands considering also groundwater abstractions from aquifers and the related exploitation index. According to the results, SWAT achieved a "very good" statistical performance (with ANSE of 0.96 and 0.78 in calibration and validation). Spatial distributions of the main hydrological processes, as surface runoff, evapotranspiration and aquifer recharge, were studied with SWAT and SIMPA obtaining similar results over the period with registers (1980-2016). During this period, the decreasing trend of rainfalls, characterised by short wet periods and long dry periods, has generated a progressive reduction of groundwater recharge. According to algorithms prediction (until 2050), this declining trend will continue reducing groundwater available to meet urban demands and increasing the exploitation index of aquifers. These results offer valuable information to authorities for assessing water accessibility and to provide water demands in karstic areas.

Parasympathetic regulation and support from family and friends predict prosocial development in U.S. Mexican-origin adolescents.

Both parasympathetic nervous system regulation and receipt of social support from close relationships contribute to prosocial development, although few studies have examined their combined influences in adolescence and particularly within racially and ethnically minoritized populations. In this longitudinal study of 229 U.S. Mexican-origin adolescents (48% female-identifying), youths reported on receipt of social support from family and friends from 10 to 16 years, had their baseline respiratory sinus arrhythmia (RSA) measured at 17 years, reported their prosocial behavior and completed the Mind in the Eyes test to assess cognitive empathy at 17 and 19 years, and reported their prosocial civic behavior (i.e., community activity) at 19 years. Family social support predicted prosocial behavior at 17 years, and friend social support predicted prosocial civic behavior at 19 years. Compared to youths with lower or higher baseline RSA, youths with moderate RSA reported more prosocial civic behavior, had greater cognitive empathy, and tended to report more general prosocial behavior at 19 years. The quadratic association between baseline RSA and cognitive empathy was stronger for youths with greater family social support. These findings are the first to extend the evidence that moderate baseline parasympathetic nervous system activity supports prosocial development into late adolescence and with the U.S. Mexican-origin community, and these findings address calls for more integrative biopsychosocial studies of prosociality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Secretory factors released from high dose radiation-activated osteoclasts increase the expression level of pain-associated neuropeptides in sensory neuronal cultures.

Stereotactic Body Radiation Therapy for lung tumors near the chest wall often causes significant chest wall pain (CWP), negatively impacting patients' quality of life. The mechanisms behind SBRT-induced CWP remain unclear and may involve multiple factors. We investigated the potential crosstalk between radiation-activated osteoclasts and sensory neurons, focusing on osteoclast-derived factors in CWP. Using the murine pre-osteoclast cell line Raw264.7, we induced differentiation with RANKL, followed by 10Gy gamma-irradiation. Conditioned media from these irradiated osteoclasts was used to treat sensory neuronal cultures from mouse dorsal root ganglia. Neuronal cultures were also directly exposed to 10Gy radiation, with and without osteoclast co-culture. Analysis of osteoclast markers and pain-associated neuropeptides was conducted using RT-qPCR and histochemical staining. Osteoclast differentiation and activity were inhibited using Osteoprotegerin and risedronate. Results showed that high-dose radiation significantly increased osteoclast size, resorption pit size, and activity biomarkers. Neurons treated with CM from irradiated osteoclasts showed increased expression of pain-associated neuropeptides CGRP and Substance P, which was mitigated by osteoprotegerin and risedronate. This study suggests that high-dose radiation enhances osteoclast activity, upregulating pain-associated neuropeptides in sensory neurons, and that inhibitors like osteoprotegerin and risedronate may offer therapeutic strategies for managing radiation-induced pain.

Advances in biomimetic AIE nanoparticles for diagnosis and phototherapy.

This minireview provides an overview of the recent advancements in the development of biomimetic Aggregation-Induced Emission (AIE) nanoparticles and their applications in disease diagnosis, phototherapy, and photoimmunotherapy. AIE nanoparticles can be engineered to enable efficient image-guided photodynamic and photothermal therapies, however, challenges related to immune defense and target specificity persist. To overcome these, coating biomimetic materials on the surface of AIE nanoparticles, which mimic the features and functions of native cells, have emerged as a promising solution. This minireview will highlight the synthesis strategies and discuss the biomedical application of biomimetic AIE nanoparticles.