LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.

Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.

Neuropathic Pain Secondary to Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Neuropathic pain in MS is a debilitating symptom that significantly impairs the quality of life for a substantial proportion of MS patients. Neuropathic pain in MS stems primarily from demyelination, axonal loss, CNS inflammation, and direct damage to the myelin sheath, leading to pain manifestations such as ongoing extremity pain, Lhermitte's phenomenon, and trigeminal neuralgia (TN). The pathophysiological mechanisms behind MS-related neuropathic pain are explored in this review, highlighting central sensitization, neural dysfunction, spinal thalamic tract dysfunction, and inflammatory processes that exacerbate neuronal damage. Neuropathic pain in MS necessitates comprehensive assessment tools and neurophysiological tests to differentiate neuropathic pain from other MS symptoms accurately. Treatment strategies for MS-related neuropathic pain encompass pharmacological interventions, including anticonvulsants and antidepressants, and emerging therapies targeting specific inflammatory processes. The review advocates for a holistic approach to management, incorporating innovative treatments and multidisciplinary strategies to address both the physical symptoms and psychosocial aspects of this disorder. This comprehensive overview underscores the importance of ongoing research into targeted therapies to improve patient outcomes and enhance the quality of life for those affected by MS.

[Molecular allergen IgE tests show neosensitizaions occurring during house dust mite specific immunotherapy].

Objective:Neosensitizations may be occur during the allergen specific immunotherapy（AIT） due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%（18/26） patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive（>0.35 kU/L） after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.

Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma.

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

Occupational low back pain among Japanese caregivers: A large-scale cross-sectional study.

BACKGROUND: Caregivers in Japan experience a high prevalence of low back pain (LBP), with age, sex, individual pain experiences, and central sensitization symptoms potentially influencing its chronic progression. OBJECTIVE: To determine the prevalence of LBP among caregivers, as well as its relation to age and sex, and explore work status, psychological factors, and central sensitization symptoms as contributing factors to chronic LBP (CLBP). METHODS: A large-scale cross-sectional survey was conducted among 1214 caregivers in 35 geriatric healthcare facilities. The survey assessed LBP and CLBP prevalence, work status, psychological factors, and central sensitization-related symptoms. Multivariate logistic regression analysis was used to identify factors influencing CLBP. RESULTS: Among 936 valid respondents, the LBP prevalence was 69.2%. No significant sex differences were found in the prevalence of LBP and CLBP. Old age, higher pain severity, and severe symptoms related to central sensitization increased the risk of CLBP. However, work status and psychological factors did not significantly contribute to CLBP. CONCLUSION: There is a high prevalence of LBP among caregivers, age and individual pain experience significantly impact CLBP. These findings emphasize the need for therapeutic strategies to manage pain intensity, especially in the acute phase, to prevent the progression to chronicity.

Ultrasensitive Photoelectrochemical Biosensor for Dual-miRNAs Detection Based on Molecular Logic Gates and Methylene Blue Sensitized ZnO@CdS@Au Nanorods.

The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the input signals and logical operations of DNA logic gates, detection and diagnosis of cancer at different stages can be achieved. For example, in the early stages, specific input signals can be designed to correspond to early specific tumor markers, thereby achieving early cancer detection. In the late stage, logic gates for multitarget detection can be designed to simultaneously detect multiple biomarkers to improve diagnostic accuracy and comprehensiveness. In this work, we constructed a dual-target-triggered DNA logic gate for anchoring DNA tetrahedra, where methylene blue was embedded in the DNA tetrahedra to sensitize ZnO@CdS@Au, achieving ultrasensitive detection of the target substance. We tested the response of AND and OR logic gates to the platform. For AND logic gates, the sensing platform only responds when both miRNAs are present. In the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. Subsequently, we used OR logic gates for miRNA detection. Even if only one target exists, the sensing platform exhibits excellent performance. Similarly, within the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. The minimum detection limit is 1.10 aM. Whether it is the need to detect multiple targets simultaneously or only one of them, we can achieve it by selecting the appropriate logic gate. This strategy holds promising application prospects in fields such as biosensing, medical diagnosis, and environmental monitoring.

Activation of NOS-cGMP pathways promotes stress-induced sensitization of behavioral responses in zebrafish.

Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in stress-induced sensitization (SIS) of behavioral responses, in which a particular stressor triggers a state of hyper-responsiveness to other stressors after an incubation period, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents SIS; blocking NOS-2 90 min after stress also prevents stress-induced sensitization, as does blocking calcium-activated potassium channels in this latter time window. Stress-induced sensitization is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce stress-induced sensitization.

A rapid spectrophotometric test for assessing skin sensitization potential of chemicals by using N-acetyl-L-cysteine methyl ester in chemico.

During the key event 1 of skin sensitization defined as covalent binding or haptenization of sensitizer to either thiol or amino group of skin proteins, a sensitizer not only covalently binds with skin proteins but also interacts with nucleophilic small molecules such as glutathione (GSH). Although GSH would not be directly associated with skin sensitization, this interaction may be applied for developing an alternative test method simulating key event 1, haptenization. Thus, the aim of the present study was to examine whether N-acetyl-L-cysteine methyl ester (NACME), a thiol-containing compound, was selected as an electron donor to determine whether NACME reacted with sensitizers. Following a reaction of NACME with a sensitizer in a 96-well plate, the remaining NACME was measured spectrophotometrically using 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Following the optimization of test conditions with two different vehicles, such as acetonitrile (ACN) and dimethyl sulfoxide (DMSO), 64 test chemicals were tested to determine the predictive capacity of current NACME test method. The results obtained showed, the predictive capacity of 94.6% sensitivity, 88.9% specificity, and 92.2% accuracy utilizing DMSO as a vehicle with a cutoff NACME depletion of 5.85%. The three parameters were also over 85% in case of ACN. These values were comparable to or better than other OECD-approved test methods. Data demonstrated that a simple thiol-containing compound NACME might constitute as a reliable candidate for identifying reactive skin sensitizers, and that this method be considered as practical method as a screening tool for assessing a chemical's tendency to initiate skin sensitization.

The potential of vascular normalization for sensitization to radiotherapy.

Radiotherapy causes apoptosis mainly through direct or indirect damage to DNA via ionizing radiation, leading to DNA strand breaks. However, the efficacy of radiotherapy is attenuated in malignant tumor microenvironment (TME), such as hypoxia. Tumor vasculature, due to the imbalance of various angiogenic and anti-angiogenic factors, leads to irregular morphology of tumor neovasculature, disordered arrangement of endothelial cells, and too little peripheral coverage. This ultimately leads to a TME characterized by hypoxia, low pH and high interstitial pressure. This deleterious TME further exacerbates the adverse effects of tumor neovascularization and weakens the efficacy of conventional radiotherapy. Whereas normalization of blood vessels improves TME and thus the efficacy of radiotherapy. In addition to describing the research progress of radiotherapy sensitization and vascular normalization, this review focuses on the strategy and application prospect of modulating vascular normalization to improve the efficacy of radiotherapy sensitization.

Pavlovian or associative sensitization and its biological significance.

Pavlovian conditioning is typically distinguished from sensitization but a Pavlovian conditional stimulus (CS) also results in sensitization. A Pavlovian CS can sensitize responding to a probe stimulus that is related to the unconditional stimulus (US) or to the US itself. Pavlovian sensitization has been studied in the defensive, sexual, and feeding systems. In Pavlovian sensitization, the focus is not on a conditional response (CR) directly elicited by the CS but on the response mode that is activated by the CS. Activation of a response mode increases the probability of particular responses and also increases reactivity to various stimuli. Pavlovian sensitization reflects this increased stimulus reactivity. Pavlovian sensitization helps uncover successful learning in situations where a conventional CR does not occur. Pavlovian sensitization also encourages broadening our conceptions of Pavlovian conditioning to include changes in afferent processes. Implications for biological fitness and for basic and translational research are discussed.

Pretransplant, Th17 dominant alloreactivity in highly sensitized kidney transplant candidates.

Introduction: Sensitization to donor human leukocyte antigen (HLA) molecules prior to transplantation is a significant risk factor for delayed access to transplantation and to long-term outcomes. Memory T cells and their cytokines play a pivotal role in shaping immune responses, thereby increasing the risk of allograft rejection among highly sensitized patients. This study aims to elucidate the precise contribution of different CD4+ memory T cell subsets to alloreactivity in highly sensitized (HS) kidney transplant recipients. Methods and results: Stimulation of peripheral blood mononuclear cells (PBMC) with various polyclonal stimulating agents to assess non-specific immune responses revealed that HS patients exhibit elevated immune reactivity even before kidney transplantation, compared to non-sensitized (NS) patients. HS patients' PBMC displayed higher frequencies of CD4+ T cells expressing IFNγ, IL4, IL6, IL17A, and TNFα and secreted relatively higher levels of IL17A and IL21 upon stimulation with PMA/ionomycin. Additionally, PBMC from HS patients stimulated with T cell stimulating agent phytohemagglutinin (PHA) exhibited elevated expression levels of IFNγ, IL4 and, IL21. On the other hand, stimulation with a combination of resiquimod (R848) and IL2 for the activation of memory B cells demonstrated higher expression of IL17A, TNFα and IL21, as determined by quantitative real-time PCR. A mixed leukocyte reaction (MLR) assay, employing third-party donor antigen presenting cells (APCs), was implemented to evaluate the direct alloreactive response. HS patients demonstrated notably higher frequencies of CD4+ T cells expressing IL4, IL6 and IL17A. Interestingly, APCs expressing recall HLA antigens triggered a stronger Th17 response compared to APCs lacking recall HLA antigens in sensitized patients. Furthermore, donor APCs induced higher activation of effector memory T cells in HS patients as compared to NS patients. Conclusion: These results provide an assessment of pretransplant alloreactive T cell subsets in highly sensitized patients and emphasize the significance of Th17 cells in alloimmune responses. These findings hold promise for the development of treatment strategies tailored to sensitized kidney transplant recipients, with potential clinical implications.

Advancing diagnostic precision: Unveiling sensitization relationships between cat, dog, and horse allergen molecules.

BACKGROUND: Recent advancements in molecular diagnostics have unveiled a multitude of allergen molecules (AMs) associated with animal sensitizations, revealing significant cross- and co-sensitization patterns among these seemingly distinct allergens. METHOD: We investigated the sensitization profiles of 120 children, sensitized to at least one of the 14 AMs from cat, dog, or horse using the Alex test, employing correlations and hierarchical clusters to explore relationship between sensitizations. RESULTS: Sensitizations to Fel d 1, Can f 4/5, and Equ c 4 differ from other cat, dog, and horse AM sensitizations, suggesting they may represent genuine sensitizations for their respective animals. High correlations were observed among various AMs, including lipocalins (Can f 1/2/6, Fel d 4/7, and Equ c 1), serum albumins (Fel d 2, Can f 3, and Equ c 3), and uteroglobins (Fel d 1 and Can f_Fd1). Hierarchical clustering of sensitizations identified two similarity clusters and one dissimilarity cluster, providing an estimation of the likelihood of cross-reactivity. Additionally, our method facilitated speculation regarding cross-, co-, or genuine sensitization. Moreover, we noted a potential increase in the number and level of sensitized animal AMs concurrent with increased sensitization to other aeroallergens with advancing age. No significant difference was detected for the presence or absence of various types of allergic comorbidities. CONCLUSION: Correlations and hierarchical clustering can unveil the extent and magnitude of cross-, co-, and genuine sensitization relationships among animal AMs. These insights can be leveraged to enhance artificial intelligence algorithms, improving diagnostic accuracy through the integration of other measures of sensitization.

Establishing central sensitization inventory cut-off values in Dutch-speaking patients with chronic low back pain by unsupervised machine learning.

BACKGROUND: Human Assumed Central Sensitization (HACS) is involved in the development and maintenance of chronic low back pain (CLBP). The Central Sensitization Inventory (CSI) was developed to evaluate the presence of HACS, with a cut-off value of 40/100. However, various factors including pain conditions (e.g., CLBP), contexts, and gender may influence this cut-off value. Unsupervised clustering approaches can address these complexities by considering diverse factors and exploring possible HACS-related subgroups. Therefore, this study aimed to determine the cut-off values for a Dutch-speaking population with CLBP based on unsupervised machine learning. METHODS: Questionnaire data covering pain, physical, and psychological aspects were collected from patients with CLBP and aged-matched healthy controls (HC). Four clustering approaches were applied to identify HACS-related subgroups based on the questionnaire data and gender. The clustering performance was assessed using internal and external indicators. Subsequently, receiver operating characteristic (ROC) analysis was conducted on the best clustering results to determine the optimal cut-off values. RESULTS: The study included 63 HCs and 88 patients with CLBP. Hierarchical clustering yielded the best results, identifying three clusters: healthy group, CLBP with low HACS level, and CLBP with high HACS level groups. The cut-off value for the overall groups were 35 (sensitivity 0.76, specificity 0.76). CONCLUSION: This study found distinct patient subgroups. An overall CSI cut-off value of 35 was suggested. This study may provide new insights into identifying HACS-related patterns and contributes to establishing accurate cut-off values.

Evaluation of the segmental distribution of pain sensitivity among patients with central sensitization associated with chronic subacromial pain syndrome: A cross-sectional study.

INTRODUCTION: Pain sensitivity is the main finding of central sensitization (CS) and can occur in patients with chronic shoulder pain. However, there is limited evidence concerning the distribution of pain sensitivity in shoulders, forearms, and legs in patients with CS associated with chronic shoulder pain. The present study aimed to determine the distribution of pain sensitivity in patients with CS associated with chronic subacromial pain syndrome (SPS). METHOD: This cross-sectional study included 58 patients with chronic SPS and CS (patient group) and 58 healthy participants (control group). The presence of CS was determined using the Central Sensitization Inventory (CSI). To determine the distribution of pain sensitivity, pressure pain threshold (PPT) measurements were performed from the shoulders, forearms, and legs. RESULTS: There was no significant difference between the two groups in terms of sociodemographic data (p > 0.05). The patient group had a significantly higher CSI score (p < 0.001) and lower PPTs in all regions (p < 0.05) than the control group. Unlike the control group, the patient group had lower PPTs on the affected side for the shoulder [mean difference (MD) 95% confidence interval (CI): 1.2 (-1.7 to -0.6)], forearm [MD 95% CI: 1.1 (-1.7 to -0.6)], and leg [MD 95% CI: 0.9 (-1.4 to -0.3)] compared with the contralateral side (p < 0.001). CONCLUSION: Pain sensitivity is more pronounced in the affected shoulder and the forearm and leg located on this side than in those on the contralateral side in patients with CS associated with chronic SPS.

Hybrid nanopotentiators with dual cascade amplification for glioma combined interventional therapy.

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system.

Modulatory Processes in Craniofacial Pain States.

Pain is a common symptom associated with many disorders affecting the craniofacial tissues that include the teeth and their supporting structures, the jaw, face and tongue muscles, and the temporomandibular joint. Most acute craniofacial pain states are easily recognized and readily treated, but chronic craniofacial pain states (e.g., temporomandibular disorders [TMD], trigeminal neuropathies, and some headaches) may be especially challenging to manage successfully. This chapter provides an overview of the processes that underlie craniofacial pain, with a focus on the pain-modulatory mechanisms operating in craniofacial tissues and in the central nervous system (CNS), including the role of endogenous chemical processes such as those involving opioids. The chapter outlines in particular findings from preclinical studies that have provided substantial information about the neural as well as nonneural (e.g., glial) processes involved in the initiation, transmission, and modulation of nociceptive signals in the trigeminal system, and also draws attention to their clinical correlates. The increased understanding gained from these preclinical studies of how nociceptive signals can be modulated will contribute to improvements in presently available therapeutic approaches to manage craniofacial pain as well as to the development of novel analgesic approaches.

Parental Exposure to Morphine Before Conception Decreases Morphine and Cocaine-Induced Locomotor Sensitization in Male Offspring.

Repeated exposure to abused drugs leads to reorganizing synaptic connections in the brain, playing a pivotal role in the relapse process. Additionally, recent research has highlighted the impact of parental drug exposure before gestation on subsequent generations. This study aimed to explore the influence of parental morphine exposure 10 days prior to pregnancy on drug-induced locomotor sensitization. Adult male and female Wistar rats were categorized into morphine-exposed and control groups. Ten days after their last treatment, they were mated, and their male offspring underwent morphine, methamphetamine, cocaine, and nicotine-induced locomotor sensitization tests. The results indicated increased locomotor activity in both groups after drug exposure, although the changes were attenuated in morphine and cocaine sensitization among the offspring of morphine-exposed parents (MEPs). Western blotting analysis revealed altered levels of D2 dopamine receptors (D2DRs) in the prefrontal cortex and nucleus accumbens of the offspring from MEPs. Remarkably, despite not having direct in utero drug exposure, these offspring exhibited molecular alterations affecting morphine and cocaine-induced sensitization. The diminished sensitization to morphine and cocaine suggested the development of a tolerance phenotype in these offspring. The changes in D2DR levels in the brain might play a role in these adaptations.

Single-cell RNA sequencing revealed the role of the Th17 pathway in the development of anti- human leukocyte antigen antibodies in a highly sensitized mouse model.

Background: The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse. Methods: For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them. Results: We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN. Conclusion: Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

A novel allocation scheme for deceased donor kidneys to balance equity and utility.

Background: Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to resolve inequity in DDKT opportunity, whether DDKT has comparable outcomes in this disadvantaged population requires further study. This study assessed these outcomes and developed a new allocation system that balances equity and utility. Methods: Patients from national and hospital cohorts from two centers in Korea were categorized as B1 to B4 (according to panel reactive antibody [PRA] positivity and ABO blood type) and A1 to A4 (based on the maximal PRA% and blood type), respectively. Competing risk and Cox regression analyses were performed to assess the effects of PRA and blood type on graft failure and mortality, respectively. Based on DDKT opportunities and posttransplant outcomes, a new scoring system for kidney allocation was developed. Results: The national and hospital cohorts included 3,311 and 819 patients, respectively, who underwent DDKT. Despite the disparities in DDKT opportunities, the graft failure rates and mortality did not differ among the different PRA and blood type groups. Furthermore, posttransplantation outcomes did not differ according to the categories with different DDKT opportunities. A new scoring system to provide additional points to disadvantaged populations was developed based on the hazard ratios for DDKT. Conclusion: A new allocation approach based on PRA and ABO blood types offers benefits to disadvantaged patients with fewer DDKT opportunities and could enhance equity without sacrificing utility in Korea, which has a long waiting time for DDKT.

IgE-Mediated Allergy and Asymptomatic Sensitization to Cannabis Allergens-Review of Current Knowledge and Presentation of Six Cases.

Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.