Tools for Screening, Predicting, and Evaluating Sepsis and Septic Shock: A Comprehensive Review.

Sepsis is characterized by life-threatening organ dysfunction due to dysregulated host response to infection. It can progress to cause circulatory and cellular/metabolic abnormalities, resulting in septic shock that may significantly increase mortality. The pathophysiology of sepsis involves a complex interplay of invading pathogens and the body's immune defense, causing alteration in normal homeostasis, eventually leading to derangements in the cellular, humoral, circulatory, and metabolic functions. Several scoring systems have been developed to rapidly predict or suspect sepsis, such as Sequential Organ Failure Assessment (SOFA), modified SOFA (mSOFA), quick SOFA (qSOFA), shock index (SI), and modified SI (mSI). Each of these scores has been utilized for triaging patients with sepsis, and as per medical advancements these scoring systems have been modified to include or exclude certain criteria to improve their clinical utility. This review aims to compare the individual scores and their usage for sepsis that may be used for laying the foundation for early recognition and prediction of sepsis and for formulating more precise definitions in the future.

Pharmacotherapy guideline concordance for major depressive disorder and its link to functioning via symptom change.

Introduction: Alleviation of symptom severity for major depressive disorder (MDD) is known to be associated with a lagged improvement of functioning. Pharmacotherapy guidelines support algorithms for MDD treatment. However, it is currently unclear whether concordance with guidelines influences functional recovery. A guideline concordance algorithm (GCA-8) was used to measure this pathway in a naturalistic clinical setting. Methods: Data from 1403 adults (67% female, 84% non-Hispanic/Latino White, mean age of 43 years) with nonpsychotic MDD from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System registry (visits from 02/01/2015 to 04/13/2021) were evaluated. Multivariable linear regression measured associations between GCA-8 and World Health Organization Disability Assessment Schedule 2.0 (WHODAS) scores. Mediation by MDD symptom severity using the Patient Health Questionnaire depression module (PHQ-9) was also evaluated. Results: This study found a statistically significant improvement in WHODAS scores (functioning) between baseline and final measures (-2 points, P < .001) within one year. A one standard deviation increase in the GCA-8 score was associated with a 0.48-point reduction in mean disability score (total effect; P = .02) with significant mediation by the change in MDD symptom severity (coefficient = -0.51, P < .001) and a nonsignificant natural direct effect of the GCA-8 independent of PHQ-9 change (coefficient = -0.02, P = .92). Conclusions: Higher pharmacotherapy guideline concordance is associated with better functioning for MDD patients; this association likely occurs through improvement in MDD symptom severity rather than directly.

First Case of Combined Carpal and Cubital Tunnel Syndromes in an Adolescent: A Case Report and Literature Review.

Carpal and cubital tunnel syndromes are the two most common compressive neuropathies, but both carpal and cubital tunnel syndromes are extremely rare in children. Therefore, the combination of carpal and cubital tunnel syndrome in the pediatric population is even more uncommon. These neuropathies have multiple causes, with the three main categories being mechanical injury, metabolic, and idiopathic. Here, we present the unique case of a 15-year-old female with no known genetic or physical risk factors who was diagnosed with atraumatic combined carpal and cubital tunnel syndrome with severe, chronic nerve entrapment and damage. After nearly two years of conservative management, the patient had a cubital tunnel and carpal tunnel release simultaneously. The transverse carpal ligament was grossly thickened intraoperatively, leading to difficulty in the identification of the median nerve. The ulnar nerve was severely compressed and flattened. Following decompression, both nerves continued to be erythematous and inflamed. After surgery, the patient had barriers to getting appropriate postoperative care. Specifically, the patient was unable to attend physical and hand therapy appointments, possibly leading to continued weakness, numbness, and intermittent pain. In our patient, the preoperative workup did not illuminate the severity of the median and ulnar nerve damage, possibly delaying surgical intervention. In addition to our case, we utilized the TriNetX database (TriNetX, Inc., Cambridge, Massachusetts, United States) to investigate the rate and treatment of compressive neuropathies in the pediatric population. The database was queried for pediatric patients who underwent carpal tunnel release, cubital tunnel release, and pediatric patients with both carpal and cubital tunnel syndrome diagnoses in childhood. We found that there were 20,819,207 pediatric patients on the TriNetX database, of whom 503 (0.002%) were diagnosed with both carpal and cubital tunnel syndrome. Based on our case and the current literature, a thorough history of pediatric patients with suspected carpal or cubital tunnel syndrome should include an evaluation of family history and activity level for pertinent risk factors. Widening the scope of the patient history could allow for more timely surgical intervention and improve long-term outcomes for the pediatric population. When evaluating children for either carpal tunnel or cubital tunnel syndrome, we recommend that healthcare providers evaluate both neuropathies simultaneously.

Industrial and Laboratory Technologies for the Chemical Recycling of Plastic Waste.

Synthetic polymers play an indispensable role in modern society, finding applications across various sectors ranging from packaging, textiles, and consumer products to construction, electronics, and industrial machinery. Commodity plastics are cheap to produce, widely available, and versatile to meet diverse application needs. As a result, millions of metric tons of plastics are manufactured annually. However, current approaches for the chemical recycling of postconsumer plastic waste, primarily based on pyrolysis, lag in efficiency compared to their production methods. In recent years, significant research has focused on developing milder, economically viable methods for the chemical recycling of commodity plastics, which involves converting plastic waste back into monomers or transforming it into other valuable chemicals. This Perspective examines both industrial and cutting-edge laboratory-scale methods contributing to recent advancements in the field of chemical recycling.

Exploring the Ramifications of Delayed Hospital Discharges: Impacts on Patients, Physicians, and Healthcare Systems.

Prolonged hospital stays can significantly impede patients' recovery, negatively affecting anything from physical health via issues like hospital-acquired infections and increased complications due to immobility to psychological health. Several studies investigated the psychosocial impact of prolonged hospital stays, revealing a variety of patient perspectives, such as feeling uncertain and frustrated about their conditions, which can erode their trust in healthcare providers. Delayed discharges not only affect patients but also have multifaceted effects on healthcare providers, potentially reducing physician efficiency and contributing to higher rates of burnout among healthcare professionals. This article investigates the consequences of delayed versus early discharge on physicians, patients, and the overall hospital system. We conducted an extensive search through PubMed and Google Scholar using the keywords "delayed discharge," "hospital discharge," and "bed blocking" to identify all the recent studies highlighting the dynamics of patient discharge. Our results support the hypothesis that reducing delayed discharge rates will not only improve patient outcomes but also have widespread fiscal impacts. This review also outlines measures to reduce delayed discharges, ultimately leading to a significant enhancement in the healthcare system.

Effects of Preoperative Glucocorticoid Use on Patients Undergoing Single-Level Lumbar Fusions: A Retrospective Propensity Score-Matched Registry Study.

Objective Spinal fusions are gaining popularity as a means of treating spinal deformity and instability from a range of pathologies. The prevalence of glucocorticoid use has also increased in recent decades, and their systemic effects are well-documented. Although commonly used in the preoperative period, the effects of steroids on outcomes among patients undergoing spinal fusions are inadequately described. This study compares the odds of developing complications among patients who underwent single-level lumbar fusions with and without preoperative glucocorticoid use in hopes of establishing more evidence-based parameters for guiding preoperative steroid use. Methods The TriNetX multi-institutional electronic health record database was used to perform a retrospective, propensity score-matched analysis of clinical outcomes of two cohorts of patients who underwent posterior or posterolateral single-level lumbar fusions with and without interbody fusion, those who used glucocorticoids for at least one week within a year of fusion and those who did not. The outcomes of interest were examined within 30 days of the operation and included death, reoperation, deep or superficial surgical site infection (SSI), pneumonia, reintubation, ventilator dependence, tracheostomy, acute kidney injury (AKI), renal insufficiency, pulmonary embolism (PE) or deep venous thrombosis (DVT), urinary tract infection (UTI), emergency department (ED) visit, sepsis, and myocardial infarction (MI). Results The odds of developing pneumonia within 30 days of spinal fusion in the cohort that used glucocorticoids within one year of operation compared to the cohort without glucocorticoid use was 0.67 (p≤0.001, 95% CI: 0.59-0.69). The odds of requiring a tracheostomy within 30 days of spinal fusion in the cohort that used glucocorticoids within one year of operation compared to the cohort without glucocorticoid use was 0.39 (p≤0.001, 95% CI: 0.26-0.60). The odds of reoperation, deep and superficial SSI, and ED visits within 30 days of operation were significantly higher for the same glucocorticoid-receiving cohort, with odds ratios of 1.4 (p=0.003, 95% CI: 1.11-1.65), 1.86 (p≤0.001, 95% CI: 1.31-2.63), 2.28 (p≤0.001, 95% CI: 1.57-3.31), and 1.25 (p≤0.001, 95% CI: 1.17-1.33), respectively. After propensity score-matching, there was no significant difference between the odds of death, DVT, PE, MI, UTI, AKI, sepsis, reintubation, and ventilator dependence between the two cohorts. Conclusion In support of much of the current literature regarding preoperative glucocorticoid use and rates of complications, patients who underwent a single-level lumbar fusion and have used glucocorticoids for at least a week within a year of operation experienced significantly higher odds of reoperation, deep and superficial SSI, and ED visits. However, these patients using glucocorticoids were also found to have lower odds of developing pneumonia, renal insufficiency, and tracheostomy requirement than those who did not use steroids within a year of surgery.

Surface-Functionalized Microgels as Artificial Antigen-Presenting Cells to Regulate Expansion of T Cells.

Artificial antigen-presenting cells (aAPCs) are currently used to manufacture T cells for adoptive therapy in cancer treatment, but a readily tunable and modular system can enable both rapid T cell expansion and control over T cell phenotype. Here, it is shown that microgels with tailored surface biochemical properties can serve as aAPCs to mediate T cell activation and expansion. Surface functionalization of microgels is achieved via layer-by-layer coating using oppositely charged polymers, forming a thin but dense polymer layer on the surface. This facile and versatile approach is compatible with a variety of coating polymers and allows efficient and flexible surface-specific conjugation of defined peptides or proteins. The authors demonstrate that tethering appropriate stimulatory ligands on the microgel surface efficiently activates T cells for polyclonal and antigen-specific expansion. The expansion, phenotype, and functional outcome of primary mouse and human T cells can be regulated by modulating the concentration, ratio, and distribution of stimulatory ligands presented on microgel surfaces as well as the stiffness and viscoelasticity of the microgels.

Cardiac MRI: An Overview of Physical Principles With Highlights of Clinical Applications and Technological Advancements.

The purpose of this review is to serve as a concise learning tool for clinicians interested in quickly learning more about cardiac magnetic resonance imaging (CMR) and its physical principles. There is heavy coverage of the basic physical fundamentals of CMR as well as updates on the history, clinical indications, cost-effectiveness, role of artificial intelligence in CMR, and examples of common late gadolinium enhancement (LGE) patterns. This literature review was performed by searching the PubMed database for the most up-to-date literature regarding these topics. Relevant, less up-to-date articles, covering the history and physics of CMR, were also obtained from the PubMed database. Clinical indications for CMR include adult congenital heart disease, cardiac ischemia, cardiomyopathies, and heart failure. CMR has a projected cost-benefit ratio of 0.58, leading to potential savings for patients. Despite its utility, CMR has some drawbacks including long image processing times, large space requirements for equipment, and patient discomfort during imaging. Artificial intelligence-based algorithms can address some of these drawbacks by decreasing image processing times and may have reliable diagnostic capabilities. CMR is quickly rising as a high-resolution, non-invasive cardiac imaging modality with an increasing number of clinical indications. Thanks to technological advancements, especially in artificial intelligence, the benefits of CMR often outweigh its drawbacks.

Implementing a Doping Approach for Poly(methyl methacrylate) Recycling in a Circular Economy.

To mitigate pollution by plastic waste, it is paramount to develop polymers with efficient recyclability while retaining desirable physical properties. A recyclable poly(methyl methacrylate) (PMMA) is synthesized by incorporating a minimal amount of an α-methylstyrene (AMS) analogue into the polymer structure. This P(MMA-co-AMS) copolymer preserves the essential mechanical strength and optical clarity of PMMA, vital for its wide-ranging applications in various commercial and high-tech industries. Doping with AMS significantly enhances the thermal, catalyst-free depolymerization efficiency of PMMA, facilitating the recovery of methyl methacrylate (MMA) with high yield and purity at temperatures ranging from 150 to 210 °C, nearly 250 K lower than current industrial standards. Furthermore, the low recovery temperature permits the isolation of pure MMA from a mixture of assorted common plastics.

Novel Quality Control Metric for the Pharmacotherapy of Major Depressive Disorder: Measuring Guideline Concordance and Its Impact on Symptom Severity.

Objective: Studies suggest that people with major depressive disorder (MDD) often receive treatment that is not concordant with practice guidelines. To evaluate this, we (1) developed a guideline concordance algorithm for MDD pharmacotherapy (GCA-8), (2) scored it using clinical data, and (3) compared its explanation of patient-reported symptom severity to a traditional concordance measure.Methods: This study evaluated 1,403 adults (67% female, 85% non-Hispanic/Latino White, mean age 43 years) with non-psychotic MDD (per ICD-10 codes), from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) registry (visits from February 1, 2015, to April 13, 2021). We (1) scored 1-year concordance using the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines and deviation from 8 pharmacotherapy-related criteria and (2) examined associations between concordance and Patient Health Questionnaire depression module (PHQ-9) scores.Results: The mean GCA-8 score was 6.37 (standard deviation [SD] = 1.30; 8.00 = perfect concordance). Among those who switched drugs (n = 671), 81% (n = 542) did not have their dose increased to the recommended maximum before switching. In our adjusted analyses, we found that a 1 SD increase in the GCA-8 was associated with a 0.78 improvement in the mean PHQ-9 score (P < .001). The comparison concordance measure was not associated with the mean PHQ-9 score (ß = -0.20; P = .20; R2 = 0.53), and adding the GCA-8 score significantly improved the model (R2 = 0.54; Vuong test P = .008).Conclusions: By measuring naturalistic MDD pharmacotherapy guideline concordance with the GCA-8, we revealed potential treatment gaps and an inverse association between guideline concordance and MDD symptom severity.

Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications.

Type I CRISPR-Cas systems utilize the RNA-guided Cascade complex to identify matching DNA targets and the nuclease-helicase Cas3 to degrade them. Among the seven subtypes, type I-C is compact in size and highly active in creating large-sized genome deletions in human cells. Here, we use four cryoelectron microscopy snapshots to define its RNA-guided DNA binding and cleavage mechanisms in high resolution. The non-target DNA strand (NTS) is accommodated by I-C Cascade in a continuous binding groove along the juxtaposed Cas11 subunits. Binding of Cas3 further traps a flexible bulge in NTS, enabling NTS nicking. We identified two anti-CRISPR proteins AcrIC8 and AcrIC9 that strongly inhibit Neisseria lactamica I-C function. Structural analysis showed that AcrIC8 inhibits PAM recognition through allosteric inhibition, whereas AcrIC9 achieves so through direct competition. Both Acrs potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells, providing the first off-switches for type I CRISPR eukaryotic genome engineering.

Changes in Polar Lipid Composition in Balsam Fir during Seasonal Cold Acclimation and Relationship to Needle Abscission.

Needle abscission in balsam fir has been linked to both cold acclimation and changes in lipid composition. The overall objective of this research is to uncover lipid changes in balsam fir during cold acclimation and link those changes with postharvest abscission. Branches were collected monthly from September to December and were assessed for cold tolerance via membrane leakage and chlorophyll fluorescence changes at -5, -15, -25, -35, and -45 °C. Lipids were extracted and analyzed using mass spectrometry while postharvest needle abscission was determined gravimetrically. Cold tolerance and needle retention each significantly (p < 0.001) improved throughout autumn in balsam fir. There were concurrent increases in DGDG, PC, PG, PE, and PA throughout autumn as well as a decrease in MGDG. Those same lipids were strongly related to cold tolerance, though MGDG had the strongest relationship (R2 = 55.0% and 42.7% from membrane injury and chlorophyll fluorescence, respectively). There was a similar, albeit weaker, relationship between MGDG:DGDG and needle retention (R2 = 24.3%). Generally, a decrease in MGDG:DGDG ratio resulted in better cold tolerance and higher needle retention in balsam fir, possibly due to increased membrane stability. This study confirms the degree of cold acclimation in Nova Scotian balsam fir and presents practical significance to industry by identifying the timing of peak needle retention. It is suggested that MGDG:DGDG might be a beneficial tool for screening balsam fir genotypes with higher needle retention characteristics.

Exploiting Activation and Inactivation Mechanisms in Type I-C CRISPR-Cas3 for Genome Editing Applications.

Type I CRISPR-Cas systems utilize the RNA-guided Cascade complex to identify matching DNA targets, and the nuclease-helicase Cas3 to degrade them. Among seven subtypes, Type I-C is compact in size and highly active in creating large-sized genome deletions in human cells. Here we use four cryo-electron microscopy snapshots to define its RNA-guided DNA binding and cleavage mechanisms in high resolution. The non-target DNA strand (NTS) is accommodated by I-C Cascade in a continuous binding groove along the juxtaposed Cas11 subunits. Binding of Cas3 further traps a flexible bulge in NTS, enabling efficient NTS nicking. We identified two anti-CRISPR proteins AcrIC8 and AcrIC9, that strongly inhibit N. lactamica I-C function. Structural analysis showed that AcrIC8 inhibits PAM recognition through direct competition, whereas AcrIC9 achieves so through allosteric inhibition. Both Acrs potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells, providing the first off-switches for controllable Type I CRISPR genome engineering.

The role of sympathetic innervation in neonatal muscle growth and neuromuscular contractures.

Neonatal brachial plexus injury (NBPI), a leading cause of pediatric upper limb paralysis, results in disabling and incurable muscle contractures that are driven by impaired longitudinal growth of denervated muscles. A rare form of NBPI, which maintains both afferent and sympathetic muscle innervation despite motor denervation, protects against contractures. We have previously ruled out a role for NRG/ErbB signaling, the predominant pathway governing antegrade afferent neuromuscular transmission, in modulating the formation of contractures. Our current study therefore investigated the contributions of sympathetic innervation of skeletal muscle in modulating NBPI-induced contractures. Through chemical sympathectomy and pharmacologic modification with a ß2 -adrenergic agonist, we discovered that sympathetic innervation alone is neither required nor sufficient to modulate contracture formation in neonatal mice. Despite this, sympathetic innervation plays an intriguing sex-specific role in mediating neonatal muscle growth, as the cross-sectional area (CSA) and volume of normally innervated male muscles were diminished by ablation of sympathetic neurons and increased by ß-adrenergic stimulation. Intriguingly, the robust alterations in CSA occurred with minimal changes to normal longitudinal muscle growth as determined by sarcomere length. Instead, ß-adrenergic stimulation exacerbated sarcomere overstretch in denervated male muscles, indicating potentially discrete regulation of muscle width and length. Future investigations into the mechanistic underpinnings of these distinct aspects of muscle growth are thus essential for improving clinical outcomes in patients affected by muscle disorders in which both length and width are affected.

Intravascular fasciitis of the scalp as a complication of ICP monitor placement: a case report and review of the literature.

BACKGROUND/IMPORTANCE: There are only 56 documented cases of intravascular fasciitis, a rare variant of nodular fasciitis. Of these cases, only 2 involved the scalp. This lesion is amenable to surgical resection, making it important to differentiate it from soft tissue malignancies of the scalp. CLINICAL PRESENTATION: We report an unusual case of intravascular fasciitis involving the scalp at the site of an intracranial pressure (ICP) monitor of a 13-year-old male patient. The lesion was surgically excised with no recurrence upon 1-month follow-up. CONCLUSION: Intravascular fasciitis is a benign, reactive proliferation of soft tissue that may arise at sites of prior trauma. It appears as a soft, painless, mobile lesion, and immunohistochemical studies are required to differentiate it from malignant lesions. The standard of care is surgical resection of the lesion.

Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis: Implications for neurocognitive and affective alterations.

Approximately 50 % of the individuals living with human immunodeficiency virus type 1 (HIV-1) are plagued by debilitating neurocognitive impairments (NCI) and/or affective alterations. Sizeable alterations in the composition of the gut microbiome, or gastrointestinal dysbiosis, may underlie, at least in part, the NCI, apathy, and/or depression observed in this population. Herein, two interrelated aims will be critically addressed, including: 1) the evidence for, and functional implications of, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals; and 2) the potential for therapeutically targeting the consequences of this dysbiosis for the treatment of HIV-1-associated NCI and affective alterations. First, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals is characterized by decreased alpha (α) diversity, a decreased relative abundance of bacterial species belonging to the Bacteroidetes phylum, and geographic-specific alterations in Bacillota (formerly Firmicutes) spp. Fundamentally, changes in the relative abundance of Bacteroidetes and Bacillota spp. may underlie, at least in part, the deficits in γ-aminobutyric acid and serotonin neurotransmission, as well as prominent synaptodendritic dysfunction, observed in this population. Second, there is compelling evidence for the therapeutic utility of targeting synaptodendritic dysfunction as a method to enhance neurocognitive function and improve motivational dysregulation in HIV-1. Further research is needed to determine whether the therapeutics enhancing synaptic efficacy exert their effects by altering the gut microbiome. Taken together, understanding gastrointestinal microbiome dysbiosis resulting from chronic HIV-1 viral protein exposure may afford insight into the mechanisms underlying HIV-1-associated neurocognitive and/or affective alterations; mechanisms which can be subsequently targeted via novel therapeutics.

Selective Cleavage of Lignin Model Compounds via a Reverse Biosynthesis Mechanism.

Selective depolymerization of lignin remains a significant challenge in biomass conversion. The biosynthesis of lignin involves the polymerization of monolignol building blocks through oxidative radical coupling reactions. A strategy for lignin degradation leverages photoredox deoxygenative radical formation to trigger reverse biosynthesis, which cleaves model compounds of the ß-O-4 and ß-5-ß-O-4 linkages to produce monolignols, precursors to flavoring compounds. This mild method preserves important oxygen functionality and serves as a platform for achieving selective lignin depolymerization.

Exploring skeletal muscle tolerance and whole-body metabolic effects of FDA-approved drugs in a volumetric muscle loss model.

Volumetric muscle loss (VML) is associated with persistent functional impairment due to a lack of de novo muscle regeneration. As mechanisms driving the lack of regeneration continue to be established, adjunctive pharmaceuticals to address the pathophysiology of the remaining muscle may offer partial remediation. Studies were designed to evaluate the tolerance and efficacy of two FDA-approved pharmaceutical modalities to address the pathophysiology of the remaining muscle tissue after VML injury: (1) nintedanib (an anti-fibrotic) and (2) combined formoterol and leucine (myogenic promoters). Tolerance was first established by testing low- and high-dosage effects on uninjured skeletal muscle mass and myofiber cross-sectional area in adult male C57BL/6J mice. Next, tolerated doses of the two pharmaceutical modalities were tested in VML-injured adult male C57BL/6J mice after an 8-week treatment period for their ability to modulate muscle strength and whole-body metabolism. The most salient findings indicate that formoterol plus leucine mitigated the loss in muscle mass, myofiber number, whole-body lipid oxidation, and muscle strength, and resulted in a higher whole-body metabolic rate (p ≤ 0.016); nintedanib did not exacerbate or correct aspects of the muscle pathophysiology after VML. This supports ongoing optimization efforts, including scale-up evaluations of formoterol treatment in large animal models of VML.

Microporogen-Structured Collagen Matrices for Embedded Bioprinting of Tumor Models for Immuno-Oncology.

Embedded bioprinting enables the rapid design and fabrication of complex tissues that recapitulate in vivo microenvironments. However, few biological matrices enable good print fidelity, while simultaneously facilitate cell viability, proliferation, and migration. Here, a new microporogen-structured (µPOROS) matrix for embedded bioprinting is introduced, in which matrix rheology, printing behavior, and porosity are tailored by adding sacrificial microparticles composed of a gelatin-chitosan complex to a prepolymer collagen solution. To demonstrate its utility, a 3D tumor model is created via embedded printing of a murine melanoma cell ink within the µPOROS collagen matrix at 4 °C. The collagen matrix is subsequently crosslinked around the microparticles upon warming to 21 °C, followed by their melting and removal at 37 °C. This process results in a µPOROS matrix with a fibrillar collagen type-I network akin to that observed in vivo. Printed tumor cells remain viable and proliferate, while antigen-specific cytotoxic T cells incorporated in the matrix migrate to the tumor site, where they induce cell death. The integration of the µPOROS matrix with embedded bioprinting opens new avenues for creating complex tissue microenvironments in vitro that may find widespread use in drug discovery, disease modeling, and tissue engineering for therapeutic use.

Cannabis use frequency and pain interference among people with HIV.

Cannabis is often used by people with HIV (PWH) for pain, yet study results are inconsistent regarding whether and how it affects pain. This study examines whether greater cannabis use frequency is associated with lower pain interference and whether cannabis use modifies the association of pain severity and pain interference among 134 PWH with substance dependence or a lifetime history of injection drug use. Multi-variable linear regression models examined the association between past 30-day cannabis use frequency and pain interference. Additional models evaluated whether cannabis use modified the association between pain severity and pain interference. Cannabis use frequency was not significantly associated with pain interference. However, in a model with interaction between cannabis use frequency and pain severity, greater cannabis use frequency attenuated the strength of the association between pain severity and pain interference (p = 0.049). The adjusted mean difference (AMD) in pain interference was +1.13, + 0.81, and +0.05 points for each 1-point increase in pain severity for those with no cannabis use, 15 days of use, and daily use, respectively. These findings suggest that attenuating the impact of pain severity on pain-related functional impairment is a potential mechanism for a beneficial role of cannabis for PWH.