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Background: Although the DSM-5 was adopted in 2013, the validity of the new substance use disorder (SUD) diagnosis and craving criterion has not been investigated systematically across substances. Methods: Adults (N = 588) who engaged in binge drinking or illicit drug use and endorsed at least one DSM-5 SUD criterion were included. DSM-5 SUD criteria were assessed for alcohol, tobacco, cannabis, cocaine, heroin, and opioids. Craving was considered positive if "wanted to use so badly that could not think of anything else" (severe craving) or "felt a very strong desire or urge to use" (moderate craving) was endorsed. Baseline information on substance-related variables and psychopathology was collected, and electronic daily assessment queried substance use for the following 90 days. For each substance, logistic regression estimated the association between craving and validators, i.e. variables expected to be related to craving/SUD, and whether association with the validators differed for DSM-5 SUD diagnosed with craving as a criterion v. without. Results: Across substances, craving was associated with most baseline validators (p values<0.05); neither moderate nor severe craving consistently showed greater associations. Baseline craving predicted subsequent use [odds ratios (OR): 4.2 (alcohol) – 234.3 (heroin); p 's ⩽ 0.0001], with stronger associations for moderate than severe craving (p 's < 0.05). Baseline DSM-5 SUD showed stronger associations with subsequent use when diagnosed with craving than without (p 's < 0.05). Conclusion: The DSM-5 craving criterion as operationalized in this study is valid. Including craving improves the validity of DSM-5 SUD diagnoses, and clinical relevance, since craving may cause impaired control over use and development and maintenance of SUD. [ABSTRACT FROM AUTHOR]

Presents information on the utilization of media-bed filtration by industries in the United States. Different forms media-bed filtration may take; Complaints leveled towards media-bed filtration; Information on the need for properly designed, and specified equipment, and equipment internals; Suggestions for managers who are using media-bed filtration. INSETS: Know your wedgewire.;How are we doing?..

Abstract Background Prolonged sedation is common in mechanically ventilated patients and is associated with increased morbidity and mortality. We sought to determine the diagnostic value of head computed tomography (CT) in mechanically ventilated patients who remain unresponsive after discontinuation of sedation. Methods A retrospective review of adult (age >18 years of age) patients consecutively admitted to the medical intensive care unit of a tertiary care medical center. Patients requiring mechanical ventilation for management of respiratory failure for longer than 72 hours were included in the study group. A group that did not have difficulty with awakening was included as a control. Results The median time after sedation was discontinued until a head CT was performed was 2 days (interquartile range 1.375–2 days). Majority (80%) of patients underwent head CT evaluation within the first 48 hours after discontinuation of sedation. Head CT was non-diagnostic in all but one patient who had a small subarachnoid hemorrhage. Twenty-five patients (60%) had a normal head CT. Head CT findings did not alter the management of any of the patients. The control group was similar to the experimental group with respect to demographics, etiology of respiratory failure and type of sedation used. However, while 37% of subjects in the control group had daily interruption of sedation, only 19% in the patient group had daily interruption of sedation (p < 0.05). Conclusion In patients on mechanical ventilation for at least 72 hours and who remain unresponsive after sedative discontinuation and with a non-focal neurologic examination, head CT is performed early and is of very limited diagnostic utility. Routine use of daily interruption of sedation is used in a minority of patients outside of a clinical trial setting though it may decrease the frequency of unresponsiveness from prolonged sedation and the need for head CT in patients mechanically ventilated for a prolonged period.

Background: A new indication for use of silver collagen oxidized regenerated cellulose (ORC) dressing in conjunction with negative pressure wound therapy (NPWT) and reticulated open cell foam (ROCF) dressings has recently become available., Objective: An in-person meeting with 7 health care providers (HCPs) was held to identify clinical care settings and appropriate use of silver collagen ORC dressings in conjunction with NPWT and ROCF dressings., Methods: Consensus statements were developed using a modified Delphi technique. An additional 25 HCPs completed an anonymous survey on the consensus statements. Consensus was defined as ≥80% agreement among survey respondents., Results: Use of silver collagen ORC dressings with NPWT and ROCF dressings was recommended in inpatient and outpatient health care settings. Use in traumatic wounds, surgical wounds, diabetic ulcers, venous leg ulcers, and pressure injuries/ulcers was supported. Use was not recommended in the presence of exposed unprotected organs or exposed unprotected vessels, when the potential for inadequate wound hemostasis exists, acutely ischemic wounds, third-degree burns, or surgically closed incisions, or with patient hypersensitivity to product components., Conclusions: Limited evidence exists on use of NPWT in conjunction with silver collagen ORC dressings. A panel developed 12 consensus statements detailing the recommended and contraindicated uses of NPWT in conjunction with silver collagen ORC dressings.

This study aimed to identify when and how eye movements change across the human lifespan to benchmark developmental biomarkers. The sample size comprised 45,696 participants, ranging in age from 6 to 80 years old ( M = 30.39; SD = 17.46). Participants completed six eye movement tests: Circular Smooth Pursuit, Horizontal Smooth Pursuit, Vertical Smooth Pursuit, Horizontal Saccades, Vertical Saccades, and Fixation Stability. These tests examined all four major eye movements (fixations, saccades, pursuits, and vergence) using 89 eye-tracking algorithms. A semi-supervised, self-training, machine learning classifier was used to group the data into age ranges. This classifier resulted in 12 age groups: 6-7, 8-11, 12-14, 15-25, 26-31, 32-38, 39-45, 46-53, 54-60, 61-68, 69-76, and 77-80 years. To provide a descriptive indication of the strength of the self-training classifier, a series of multiple analyses of variance (MANOVA) were conducted on the multivariate effect of the age groups by test set. Each MANOVA revealed a significant multivariate effect on age groups ( p < 0.001). Developmental changes in eye movements across age categories were identified. Specifically, similarities were observed between very young and elderly individuals. Middle-aged individuals (30s) generally showed the best eye movement metrics. Clinicians and researchers may use the findings from this study to inform decision-making on patients' health and wellness and guide effective research methodologies.

Purpose: Major depressive disorder (MDD) disproportionately affects those living with autism spectrum disorder (ASD) and is associated with significant impairment and treatment recidivism., Methods: We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days). This prospective open-label 12-week trial included 10 subjects with a mean age of 21.5 years, randomized to receive unilateral or bilateral stimulation of the dorsolateral prefrontal cortex., Results: One participant dropped out of the study due to intolerability. In both treatment arms, depressive symptoms, scored on the Hamilton Depression Rating Scale scores, diminished substantially. At 12 weeks post-treatment, full remission was sustained in 5 subjects and partial remission in 3 subjects. Treatment with ATBS, regardless of the site of stimulation, was associated with a significant, substantial, and sustained improvement in depressive symptomatology via the primary outcome measure, the Hamilton Depression Rating Scale. Additional secondary measures, including self-report depression scales, fluid cognition, and sleep quality, also showed significant improvement. No serious adverse events occurred during the study. Mild transient headaches were infrequently reported, which are expected side effects of ATBS., Conclusion: Overall, ATBS treatment was highly effective and well-tolerated in individuals with ASD and co-occurring MDD. The findings support the need for a larger, sham-controlled randomized controlled trial to further evaluate efficacy of ATBS in this population., (© 2024. The Author(s).)

It is common for community-based healthcare providers (CHPs)-many of whom have not received specialised training in wound care-to deliver initial and ongoing management for various wound types and diverse populations. Wounds in any setting can rapidly transition to a stalled, hard-to-heal wound (HTHW) that is not following a normal healing trajectory. Failure to recognise or address issues that cause delayed healing can lead to increased costs, healthcare utilisation and suffering. To encourage early intervention by CHPs, a panel of wound care experts developed actionable evidence-based recommendations for CHPs delineating characteristics and appropriate care in identifying and treating HTHWs. A HTHW is a wound that fails to progress towards healing with standard therapy in an orderly and timely manner and should be referred to a qualified wound care provider (QWCP) for advanced assessment and diagnosis if not healed or reduced in size by 40%-50% within 4 weeks. HTHWs occur in patients with multiple comorbidities, and display increases in exudate, infection, devitalised tissue, maceration or pain, or no change in wound size. CHPs can play an important initial role by seeing the individual's HTHW risk, addressing local infection and providing an optimal wound environment. An easy-to-follow one-page table was developed for the CHP to systematically identify, evaluate and treat HTHWs, incorporating a basic toolkit with items easily obtainable in common office/clinic practice settings. A flow chart using visual HTHW clinical cues is also presented to address CHPs with different learning styles. These tools encourage delivery of appropriate early interventions that can improve overall healthcare efficiency and cost., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The purpose of this study was to investigate the difference in oculomotor functioning between Olympic-level contact and non-contact sports participants. In total, 67 male and female Olympic-level contact ( n  = 27) and non-contact ( n  = 40) athletes completed oculomotor tasks, including Horizontal Saccade (HS), Circular Smooth Pursuit (CSP), Horizontal Smooth Pursuit (HSP), and Vertical Smooth Pursuit (VSP) using a remote eye tracker. No significant differences for sex or age occurred. Each variable indicated higher scores for contact compared to non-contact athletes ( p < .05) except for VSP Pathway differences and CSP Synchronization. A logistic regression was performed to determine the degree that HS measures, CSP synchronization, and VSP pathway predicted sport type. The model was significant, χ 2 (6) = 37.08, p < .001, explaining 57.4% of the variance and correctly classified 88.1% of cases. The sensitivity was 87.5% and specificity was 88.9%. CSP synchronization did not increase the likelihood of participating in a contact sport. This was the first study to identify oculomotor differences between Olympic athletes of contact and non-contact sports, which adds to the growing evidence that oculomotor functioning may be a reliable, quick, real-time tool to help detect mTBI in sport.

Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor-infiltrating T and B cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non-OMAS-associated neuroblastomas. We found greater B and T cell infiltration in OMAS-associated tumors compared to controls and showed that both were polyclonal expansions. Tertiary lymphoid structures (TLSs) were enriched in OMAS-associated tumors. We identified significant enrichment of the major histocompatibility complex (MHC) class II allele HLA-DOB ∗ 01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal auto-reactive B lymphocytes act as antigen-presenting cells and drive TLS formation, thereby supporting both sustained polyclonal T cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Deep learning (DL) models can harness electronic health records (EHRs) to predict diseases and extract radiologic findings for diagnosis. With ambulatory chest radiographs (CXRs) frequently ordered, we investigated detecting type 2 diabetes (T2D) by combining radiographic and EHR data using a DL model. Our model, developed from 271,065 CXRs and 160,244 patients, was tested on a prospective dataset of 9,943 CXRs. Here we show the model effectively detected T2D with a ROC AUC of 0.84 and a 16% prevalence. The algorithm flagged 1,381 cases (14%) as suspicious for T2D. External validation at a distinct institution yielded a ROC AUC of 0.77, with 5% of patients subsequently diagnosed with T2D. Explainable AI techniques revealed correlations between specific adiposity measures and high predictivity, suggesting CXRs' potential for enhanced T2D screening., (© 2023. The Author(s).)

The T cell receptor is generated by a process of random and imprecise somatic recombination. The number of possible T cell receptors which this process can produce is enormous, greatly exceeding the number of T cells in an individual. Thus, the likelihood of identical TCRs being observed in multiple individuals (public TCRs) might be expected to be very low. Nevertheless such public TCRs have often been reported. In this study we explore the extent of TCR publicity in the context of acute resolving Lymphocytic choriomeningitis virus (LCMV) infection in mice. We show that the repertoire of effector T cells following LCMV infection contains a population of highly shared TCR sequences. This subset of TCRs has a distribution of naive precursor frequencies, generation probabilities, and physico-chemical CDR3 properties which lie between those of classic public TCRs, which are observed in uninfected repertoires, and the dominant private TCR repertoire. We have named this set of sequences "hidden public" TCRs, since they are only revealed following infection. A similar repertoire of hidden public TCRs can be observed in humans after a first exposure to SARS-COV-2. The presence of hidden public TCRs which rapidly expand following viral infection may therefore be a general feature of adaptive immunity, identifying an additional level of inter-individual sharing in the TCR repertoire which may form an important component of the effector and memory response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mark, Reich-Zeliger, Greenstein, Biram, Chain, Friedman and Madi.)

Introduction: VLUs are associated with prolonged wound healing, high recurrence rates, and fragile periwound skin., Objective: Skin protectant use with wound dressings and multilayer compression wraps was examined., Methods: Deidentified retrospective patient data were assessed. Patients received endovenous ablation, followed by application of zinc barrier cream to periwound skin before wound dressing and multilayer compression wrap use. Dressings were changed every 7 days, and zinc barrier cream reapplied. After 3 weeks, advanced elastomeric skin protectant use was initiated due to periwound skin injury during zinc barrier cream removal. Topical wound dressing and compression wrap use was continued. Wound healing and periwound skin condition were monitored., Results: Five patients presented for care with medial ankle VLUs. Within 3 weeks of zinc barrier cream use, unwanted product buildup was noted and removal often led to epidermal stripping. Skin protectant use was changed to advanced elastomeric skin protectant. All patients showed periwound skin improvement. Epidermal stripping was not observed with advanced elastomeric skin protectant, and the product did not require removal., Conclusions: In these 5 patients, advanced elastomeric skin protectant use under wound dressings and multilayer compression wraps resulted in improved periwound skin and reduced erythema compared with zinc barrier cream use.

One of the feats of adaptive immunity is its ability to recognize foreign pathogens while sparing the self. During maturation in the thymus, T cells are selected through the binding properties of their antigen-specific T-cell receptor (TCR), through the elimination of both weakly (positive selection) and strongly (negative selection) self-reactive receptors. However, the impact of thymic selection on the TCR repertoire is poorly understood. Here, we use transgenic Nur77-mice expressing a T-cell activation reporter to study the repertoires of thymic T cells at various stages of their development, including cells that do not pass selection. We combine high-throughput repertoire sequencing with statistical inference techniques to characterize the selection of the TCR in these distinct subsets. We find small but significant differences in the TCR repertoire parameters between the maturation stages, which recapitulate known differentiation pathways leading to the CD4 + and CD8 + subtypes. These differences can be simulated by simple models of selection acting linearly on the sequence features. We find no evidence of specific sequences or sequence motifs or features that are suppressed by negative selection. These results favour a collective or statistical model for T-cell self non-self discrimination, where negative selection biases the repertoire away from self recognition, rather than ensuring lack of self-reactivity at the single-cell level., Competing Interests: FC, AR, EG, SR, BC, TM, NF No competing interests declared, AW Senior editor, eLife, (© 2023, Camaglia, Ryvkin et al.)

Background: Exudate pooling is the collection of wound fluid in the wound bed. Wounds with irregular depth, pockets, or cavities can create a dead space between the dressing and the wound bed where exudate can accumulate. Exudate pooling could lead to increased risk of infection or biofilm formation, maceration of the periwound skin, and delayed wound healing., Purpose: This article aims to offer a simplified yet practical summary for the prevention and management of exudate pooling by using advanced wound dressings., Methods: Following a review of published literature, consensus statements, and best practice guidelines, the authors put their learnings into practice by translating the findings into a practical guide for the prevention and management of exudate pooling., Results: Nearly half (49.6%) of all wounds have depth beyond the epidermis (0.22 cm), a characteristic that increases the risk of exudate pooling. In addition, approximately 12% of chronic wounds are undermined by tunneling or cavities underneath the skin where exudate could pool. Appropriate dressing selection can help manage exudate and prevent exudate pooling. In particular, dressings that provide a moist environment, manage the dead space, and maintain close contact with the wound bed may help reduce the risks associated with exudate pooling. A practical guide is presented that could be used by nurses at all levels to help select appropriate dressings., Conclusion: This practical guide could help prevent and manage exudate pooling and associated risk factors.

Objective: The diagnostic criteria for opioid use disorder, originally developed for heroin, did not anticipate the surge in prescription opioid use and the resulting complexities in diagnosing prescription opioid use disorder (POUD), including differentiation of pain relief (therapeutic intent) from more common drug use motives, such as to get high or to cope with negative affect. The authors examined the validity of the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5 opioid version, an instrument designed to make this differentiation., Methods: Patients (N=606) from pain clinics and inpatient substance treatment who ever received a ≥30-day opioid prescription for chronic pain were evaluated for DSM-5 POUD (i.e., withdrawal and tolerance were not considered positive if patients used opioids only as prescribed, per DSM-5 guidelines) and pain-adjusted POUD (behavioral/subjective criteria were not considered positive if pain relief [therapeutic intent] was the sole motive). Bivariate correlated-outcome regression models indicated associations of 10 validators with DSM-5 and pain-adjusted POUD measures, using mean ratios for dimensional measures and odds ratios for binary measures., Results: The prevalences of DSM-5 and pain-adjusted POUD, respectively, were 44.4% and 30.4% at the ≥2-criteria threshold and 29.5% and 25.3% at the ≥4-criteria threshold. Pain adjustment had little effect on prevalence among substance treatment patients but resulted in substantially lower prevalence among pain treatment patients. All validators had significantly stronger associations with pain-adjusted than with DSM-5 dimensional POUD measures (ratios of mean ratios, 1.22-2.31). For most validators, pain-adjusted binary POUD had larger odds ratios than DSM-5 measures., Conclusions: Adapting POUD measures for pain relief (therapeutic intent) improved validity. Studies should investigate the clinical utility of differentiating between therapeutic and nontherapeutic intent in evaluating POUD diagnostic criteria.

We systematically examine the receptor repertoire in T cell subsets in young, adult, and LCMV-infected mice. Somatic recombination generates diversity, resulting in the limited overlap between nucleotide sequences of different repertoires even within the same individual. However, statistical features of the repertoire, quantified by the V gene and CDR3 k-mer frequency distributions, are highly conserved. A hierarchy of immunological processes drives the evolution of this structure. Intra-thymic divergence of CD4+ and CD8+ lineages imposes subtle but dominant differences observed across repertoires of all subpopulations in both young and adult mice. Differentiation from naive through memory to effector phenotype imposes an additional gradient of repertoire diversification, which is further influenced by age in a complex and lineage-dependent manner. The distinct repertoire of CD4+ regulatory T cells is more similar to naive cells in young mice and to effectors in adults. Finally, we describe divergent (naive and memory) and convergent (CD8+ effector) evolution of the repertoire following acute infection with LCMV. This study presents a quantitative framework that captures the structure of the repertoire in terms of its fundamental statistical properties and describes how this structure evolves as individual T cells differentiate, migrate and mature in response to antigen exposure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mark, Reich-Zeliger, Greenstein, Reshef, Madi, Chain and Friedman.)

Background: DSM-5 tobacco use disorder (TUD) nosology differs from DSM-IV nicotine dependence (ND) by including craving and DSM-IV abuse criteria, a lower threshold (≥ 2 criteria), and severity levels (mild; moderate; severe). We assessed concurrent and prospective validity of the DSM-5 TUD diagnosis and severity and compared validity with DSM-IV ND diagnosis., Methods: The sample included U.S. adults with current problematic substance use and past year cigarette smoking (N = 396). Baseline assessment collected information on DSM-IV ND and DSM-5 TUD criteria, smoking-related variables, and psychopathology. Over the following 90 days, electronic daily assessments queried smoking and cigarette craving. Variables expected to be related to TUD were validators: cigarette consumption, cigarette craving scale, Fagerström Test for Nicotine Dependence, and psychiatric disorders. Regression models estimated the association of each validator with DSM-5 TUD and severity levels, and differential association between DSM-5 TUD and DSM-IV ND diagnoses., Results: DSM-5 TUD and DSM-IV ND were associated with most baseline validators (p-values < 0.05), with significantly stronger associations with DSM-5 TUD for number of days smoked (p = 0.023) and cigarette craving scale (p = 0.007). Baseline DSM-5 TUD and DSM-IV ND predicted smoking and craving on any given day during follow-up, with stronger associations for DSM-5 TUD (association difference [95% CI%]: any smoking, 0.53 [0.27, 0.77]; number of cigarettes smoked, 1.36 [0.89, 1.78]; craving scale, 0.19 [0.09, 0.28]). Validators were associated with TUD severity in a dose-dependent manner., Conclusion: DSM-5 TUD diagnostic measures as operationalized here demonstrated concurrent and prospective validity. Inclusion of new criteria, particularly craving, improved validity and clinical relevance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Negative pressure wound therapy (NPWT) is applied using a foam dressing and an adhesive acrylic drape to create a seal. Removal of this drape can be painful and may play a role in periwound skin breakdown during dressing changes. A novel silicone-acrylic hybrid drape (HA-drape) has been developed for use with NPWT to allow for repositioning after initial placement and easier removal., Objective: This retrospective case series reports on the use of HA-drape in 4 patients who experienced periwound skin breakdown. The goal was to minimize skin breakdown while maintaining a seal on the dressing., Materials and Methods:  Four patients with mild to moderate periwound skin breakdown were selected to receive NPWT with HA-drape. Negative pressure wound therapy was applied using a reticulated open cell foam dressing followed by placement of HA-drape to create a seal. Negative pressure wound therapy was initiated at -125 mm Hg with dressing changes occurring every 2 days. Wound healing, periwound healing, and patient-reported pain were assessed at dressing changes., Results: All 4 patients showed significant periwound skin improvement after the first dressing change. All patients reported a decrease in pain with dressing removal., Conclusions: In these 4 patients' wounds, use of NPWT with HA-drape resulted in intact periwound with improved periwound skin healing and reduction in patient-reported pain associated with dressing changes.

Neoantigens are now recognized drivers of the antitumor immune response. Recurrent neoantigens, shared among groups of patients, have thus become increasingly coveted therapeutic targets. Here, we report on the data-driven identification of a robustly presented, immunogenic neoantigen that is derived from the combination of HLA-A*01:01 and RAS.Q61K. Analysis of large patient cohorts indicated that this combination applies to 3% of patients with melanoma. Using HLA peptidomics, we were able to demonstrate robust endogenous presentation of the neoantigen in 10 tumor samples. We detected specific reactivity to the mutated peptide within tumor-infiltrating lymphocytes (TILs) from 2 unrelated patients, thus confirming its natural immunogenicity. We further investigated the neoantigen-specific clones and their T cell receptors (TCRs) via a combination of TCR sequencing, TCR overexpression, functional assays, and single-cell transcriptomics. Our analysis revealed a diverse repertoire of neoantigen-specific clones with both intra- and interpatient TCR similarities. Moreover, 1 dominant clone proved to cross-react with the highly prevalent RAS.Q61R variant. Transcriptome analysis revealed a high association of TCR clones with specific T cell phenotypes in response to cognate melanoma, with neoantigen-specific cells showing an activated and dysfunctional phenotype. Identification of recurrent neoantigens and their reactive TCRs can promote "off-the-shelf" precision immunotherapies, alleviating limitations of personalized treatments.

A T-cell receptor (TCR) with optimal avidity to a tumor antigen can be used to redirect T cells to eradicate cancer cells via adoptive cell transfer. Cancer testis antigens (CTAs) are attractive targets because they are expressed in the testis, which is immune-privileged, and in the tumor. However, CTAs are self-antigens and natural TCRs to CTAs have low affinity/avidity due to central tolerance. We previously described a method of directed evolution of TCR avidity using somatic hypermutation. In this study, we made several improvements to this method and enhanced the avidity of the hT27 TCR, which is specific for the cancer testis antigen HLA-A2-MAGE-A1 278-286 . We identified eight point mutations with varying degrees of improved avidity. Human T cells transduced with TCRs containing these mutations displayed enhanced tetramer binding, IFN-γ and IL2 production, and cytotoxicity. Most of the mutations have retained specificity, except for one mutant with extremely high avidity. We demonstrate that somatic hypermutation is capable of optimizing avidity of clinically relevant TCRs for immunotherapy., (© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Background and Aims: Ecological studies have suggested that Cannabis legalization might have led to a decrease in opioid overdose deaths. Such studies do not provide information about whether individuals are substituting Cannabis for opioids at different points in time. The current study assessed the magnitude of the daily association between Cannabis and opioid use in individual adults with and without pain who use non-medical opioids., Design: Prospective cohort study., Setting: The greater New York area and a suburban inpatient addiction program., Participants: Adults with problem substance use who use non-medical opioids, recruited from May 2016-June 2019. The analytical sample included 13 271 days of observation among 211 participants (64% male, 41% white, 78% unmarried, 80% unemployed, mean age 43 years)., Measurements: Participants completed interviewer- and self-administered computerized surveys, and then responded to an interactive voice response (IVR) system daily for the following 90 days. The main exposures, Cannabis use and pain, were defined as responding affirmatively to the IVR question: 'Did you use Cannabis yesterday?' and endorsing moderate or severe pain at baseline, respectively. The main outcome, non-medical or illicit opioid use during 90-day follow-up, was defined as responding affirmatively to IVR question: 'Did you use heroin yesterday?' or 'Did you use prescription opioids more than prescribed or without a prescription yesterday?'., Findings: The mean IVR completion rate was 70%. The unadjusted odds ratio (aOR) indicating same-day use of Cannabis and opioids was 2.00 [95% confidence interval (CI) = 1.54-2.59]. Controlling for demographic characteristics, recruitment method, opioid types at baseline and pain, the aOR was 1.86 (95% CI = 1.44-2.41). A test of interaction between pain and Cannabis use to determine if the association of Cannabis with opioid use differed between people with moderate-to-severe pain and less-than-moderate pain was inconclusive., Conclusions: Among US adults with problem substance use who use non-medical opioids, the odds of opioid use appear to be approximately doubled on days when Cannabis is used. This relationship does not appear to differ between people with moderate or more severe pain versus less than moderate pain, suggesting that Cannabis is not being used as a substitute for illegal opioids., (© 2020 Society for the Study of Addiction.)

Background: Pressure ulcers/injuries (PU/Is) negatively affect patients by causing pain and increasing morbidity and mortality risks. Care teams have a heightened sense of awareness of the condition and may feel confident in their ability to appropriately identify and manage PU/Is, but the potential for, and consequences of, a misdiagnosis always should be considered., Purpose: The purpose of this compendium is to describe and illustrate conditions that may mimic PU/Is., Methods: Advanced practice wound care nurses were asked to identify and describe conditions that may mimic PU/Is. Permission was obtained from all patients to use their cases and photos in this article., Results: Sixteen (16) different skin and wound presentations resulting from vascular diseases, systemic infections, trauma, cancer, autoimmune disorders, coagulopathies, and multisystem organ dysfunction were identified and described., Conclusion: A complete patient history and assessment will help prevent misidentification of the etiology of a skin lesion or wound and misdiagnosis of these lesions as PU/Is.