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It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.

Sensory adaptation is the process whereby brain circuits adjust neuronal activity in response to redundant sensory stimuli. Although sensory adaptation has been extensively studied for individual neurons on timescales of tens of milliseconds to a few seconds, little is known about it over longer timescales or at the population level. We investigated population-level adaptation in the barrel field of the mouse somatosensory cortex (S1BF) using in vivo two-photon calcium imaging and Neuropixels recordings in awake mice. Among stimulus-responsive neurons, we found both adapting and facilitating neurons, which decreased or increased their firing, respectively, with repetitive whisker stimulation. The former outnumbered the latter by 2:1 in layers 2/3 and 4; hence, the overall population response of mouse S1BF was slightly adapting. We also discovered that population adaptation to one stimulus frequency (5 Hz) does not necessarily generalize to a different frequency (12.5 Hz). Moreover, responses of individual neurons to repeated rounds of stimulation over tens of minutes were strikingly heterogeneous and stochastic, such that their adapting or facilitating response profiles were not stable across time. Such representational drift was particularly striking when recording longitudinally across 8-9 days, as adaptation profiles of most whisker-responsive neurons changed drastically from one day to the next. Remarkably, repeated exposure to a familiar stimulus paradoxically shifted the population away from strong adaptation and toward facilitation. Thus, the adapting vs. facilitating response profile of S1BF neurons is not a fixed property of neurons but rather a highly dynamic feature that is shaped by sensory experience across days.

IntroductionWhile a specific number and type of antigens are recognized to detect perennial inhalant allergies, the optimal number and combination of allergens to reliably identify seasonal allergic sensitization is unclear due to limited national data. This study analyzed aeroallergen testing data from a large US clinical reference laboratory to provide guidance for optimizing seasonal allergen test selection.MethodsThe 2019 serum IgE tests for seasonal inhalant allergens were identified from the Quest Diagnostics database. Patients with results for at least 1 of 31 seasonal allergens across 4 allergen classes (11 trees, 7 weeds, 5 grasses, and 8 molds) were analyzed. A step-by-step conditional approach was employed to determine the minimum number and species of allergens needed to identify at least 98% of sensitized patients for each class.ResultsOf 88,042 patients tested for ≥1 seasonal allergen, 1.5%, 1.8%, 1.3%, and 1.6% were tested for all trees, weeds, grasses, and molds, respectively. Of those tested for all allergens within a class, 40.4%, 38.6%, 29.5%, and 21.2% were sensitized to at least one tree, weed, grass, or mold allergen, respectively. Identification of ≥98% of sensitized patients within a class required 8 allergens for trees (mountain cedar, maple box elder, walnut, white ash, elm, birch, cottonwood, and hickory/pecan), 5 for weeds (common ragweed short, rough pigweed, English plantain, lamb's quarters/goosefoot, and Russian thistle), 3 for grasses (June/Kentucky blue grass, Johnson grass, and Bermuda grass), and 7 for molds (Alternaria alternata, Aspergillus fumigatus, Mucor racemosus, Epicoccum purpurascens, Penicillium notatum, Helminthosporium halodes, and Fusarium moniliforme).ConclusionA minimum of 23 antigens is required to optimally detect sensitization to four classes of seasonal allergens (i.e., ≥98% identification). The addition of these allergens to unique perennial allergens (cat, dog, mouse, cockroach, and 2 dust mite species) results in a comprehensive elucidation of inhalant allergen sensitization. This knowledge provides a pivotal guide for clinical laboratories as they construct allergen panels to optimize diagnostic yield.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.

Photodynamic therapy (PDT) stands out as a highly promising modality for tumor treatment, yet previous works have primarily centered around either boosting the production of reactive oxygen species (ROS) in tumor tissues or restricting it in normal tissues. The current challenge lies in the urgent need to achieve precise modulation of ROS production by simultaneously controlling both aspects. To achieve this goal, a precise PDT platform through a “locking‐unlocking‐boosting” ROS production strategy is presented, in which the generation of ROS is modulated by bidirectionally regulating the upconversion luminescence (UCL) of lanthanide‐doped nanoparticles (LnNPs), thus ROS production is “locked” in normal tissues but “boosted” in tumor tissues. In detail, by introducing an energy acceptor BHQ3, the UCL is initially quenched to prevent Chlorin e6 (Ce6) from generating ROS. However, under the tumor microenvironment with overexpressed miR‐21, LnNPs are sequestered from BHQ3 to “unlock” ROS generation and then assembled with QDs@B2, which functions as an antenna to sensitize LnNPs luminescence, to further “boost” ROS generation. With the assistance of spherical nucleic acids, this therapeutic agent effectively traverses the blood‐brain barrier (BBB), enabling efficient PDT for glioblastoma. [ABSTRACT FROM AUTHOR]

Background: Mechanisms underlying psychostimulant euphoria remain poorly understood. In adult rats, positive emotional states are associated with alterations in 50-kHz ultrasonic vocalizations (USVs): specifically, "trill" calls are promoted over "flat" calls. Here, we investigated the effects of acute and repeated cocaine administration, and—based on previous findings with amphetamine—their possible dependence on beta-adrenergic receptors. Methods: Adult male Long-Evans rats received intraperitoneal drug or saline injections before daily USV recording. Fourteen 50-kHz call subtypes were analyzed. In Experiments 1 and 2, cocaine (1–10 mg/kg) and propranolol (10 mg/kg) were tested alone. In Experiment 3, propranolol/cocaine interactions were sought within a conditioned place preference (CPP) procedure. Experiment 4 investigated acute and chronic cocaine effects (Phase 1), and propranolol/cocaine interactions either in an open field (Phase 2) or within a CPP procedure (Phase 3). Results: In drug-naïve animals, cocaine increased the 50-kHz call rate, with sensitization developing rapidly. After more extended exposure, cocaine now also increased the relative prevalence of trill versus flat calls; effects on other subtypes were also revealed. The beta-blocker propranolol prevented neither cocaine CPP nor cocaine effects on USV emission or locomotion but exerted significant USV-related effects when given alone. CPP magnitude and USV-related measures were uncorrelated. Conclusions: With long-term intraperitoneal administration, cocaine can alter the relative prevalence of several 50-kHz call subtypes; its ability to promote trill versus flat calls, in particular, is consistent with a positive affect interpretation. Cocaine's behavioral effects (i.e., USV-related, locomotor, CPP) appear independent of beta-adrenergic receptor activity. [ABSTRACT FROM AUTHOR]

Objectives: We evaluate the presence of sensitization-associated symptoms and neuropathic pain features and identify if there is an association between these symptoms and pressure pain sensitivity, pain, and related-disability in lateral elbow tendinopathy. Methods: Thirty-seven (43% women, age: 45.5 ± 9.5 years) patients with lateral elbow tendinopathy completed: demographic (i.e. age, height, and weight); clinical (i.e. pain history, pain intensity, and Disabilities of the Arm, Shoulder and Hand); and psychophysical (i.e. pressure pain thresholds at the elbow, cervical spine, hand, and leg) outcomes, and the Central Sensitization Inventory and Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaires. Step-wise multiple linear regression models were performed to identify predictors of sensitization- or neuropathic-associated symptoms. Results: Six (16%) patients exhibited sensitization-associated symptoms (mean: 46.5, SD: 6.1), whereas 13 (35%) patients showed neuropathic-associated symptoms (mean: 13.5; SD: 1.4). Sensitization-associated symptoms were positively associated with neuropathic-associated symptoms (r = 0.538, P =.001) and negatively associated with pressure pain thresholds at the leg (r = -0.378, P =.021). Neuropathic-associated symptoms were positively associated with related-disability (r = 0.479, P =.003) and negatively associated with pressure pain threshold at the elbow (r = -0.394, P =.017). Stepwise regression analyses revealed that neuropathic-like symptoms explained 26.8% of the variance of sensitization symptoms (r2: 0.268), whereas pressure pain threshold at the elbow explained an additional 6.6% to neuropathic-like symptoms (r2: 0.334). Conclusion: This explorative study identified sensitization- and neuropathic-associated symptoms in 16% and 35% of the people with lateral elbow tendinopathy. Sensitization- and neuropathic-associated symptoms were associated. Pressure pain sensitivity at the elbow (peripheral sensitization) was associated with neuropathic -associated symptoms. [ABSTRACT FROM AUTHOR]

The present paper contains the preparation of QDs sensitized on TiO2 thin film as a photoanode for solar cell applications. The photoanode is developed by copper sulfide quantum dots (CuS QDs) on TiO2 thin films using the successive ionic layer adsorption and reaction (SILAR). CuS QDs act as sensitizer because of its strong visible light absorption. Fabrication process comprises sensitizing CuS QDs on the surface of TiO2 thin films controlled by 5 and 10 SILAR cycles. XRD study indicates the crystallite size of TiO2/CuS QDs thin films is 11.6 and 13.7 nm for 5 and 10 cycles (cys), respectively. The outcome of UV-DRS and photoluminescence indicates the enhanced light absorption, reduction in bandgap and suppression of electron–hole pair recombination. The HR-TEM image revealed that the diameter of the TiO2 is 10 nm and surroundings core-like CuS particles are observed. The TiO2/CuS QDs (10 cys) configuration showed a better photoelectrochemical efficiency of 2.55% at 30 mW cm−2 light intensity. [ABSTRACT FROM AUTHOR]

Lipschütz ulcer (LU) is a condition known for painful vulvar ulcers, typically affecting young women and often linked to infectious agents. Recent reports have indicated a potential connection between LU and COVID‐19 vaccination, particularly after the second or booster doses. This study presents a case of LU following the first dose of tozinameran in a young woman who had a previous SARS‐CoV‐2 infection and investigates similar cases globally. An 18‐year‐old woman experienced vulvar pain and ulcers 2‐days after her initial COVID‐19 vaccine dose. After ruling out infections through serological tests, a diagnosis of LU was made, and her symptoms resolved after 10 days. A literature search and VigiBase® analysis revealed 11 cases of LU following COVID‐19 vaccination, and 519 vulvovaginal ulcer cases associated with these vaccines were identified in Vigibase®, with a median onset of 2 days. Most LU cases occurred after the second dose or booster shots. The primary hypothesis for this association is a type 3 hypersensitivity reaction mediated by immune complexes, possibly triggered by prior exposure, as many cases occurred after the second dose. Interestingly, the presented case suggests that prior COVID‐19 infection could serve as sensitization. In conclusion, this study highlights the potential occurrence of LU after the initial COVID‐19 vaccine dose in young patients with prior COVID‐19 infection. While the risk of recurrence after subsequent vaccinations or infections remains uncertain, the benefits of vaccination outweigh the risks. Clinicians and patients should be aware of this potential issue to make informed decisions regarding vaccination. [ABSTRACT FROM AUTHOR]

Simple Summary: Small cell lung cancer (SCLC) is a deadly cancer that is treated by chemo- and radiotherapy, which work by damaging DNA. However, most SCLC patients will develop resistance to these treatments, resulting in a poor outlook with few effective treatment options available. This review summarizes our understanding of the causes of treatment resistance and the treatments which have been studied to overcome resistance. While there is still much to be understood, new methods being developed may improve our ability to study this disease and find effective treatments. Background: Small cell lung cancer (SCLC) is a lethal form of lung cancer with few treatment options and a high rate of relapse. While SCLC is initially sensitive to first-line DNA-damaging chemo- and radiotherapy, relapse disease is almost universally therapy-resistant. As a result, there has been interest in understanding the mechanisms of therapeutic resistance in this disease. Conclusions: Progress has been made in elucidating these mechanisms, particularly as they relate to the DNA damage response and SCLC differentiation and transformation, leading to many clinical trials investigating new therapies and combinations. Yet there remain many gaps in our understanding, such as the effect of epigenetics or the tumor microenvironment on treatment response, and no single mechanism has been found to be ubiquitous, suggesting a significant heterogeneity in the mechanisms of acquired resistance. Nevertheless, the advancement of techniques in the laboratory and the clinic will improve our ability to study this disease, especially in patient populations, and identify methods to surmount therapeutic resistance. [ABSTRACT FROM AUTHOR]

Background: The α‐Gal syndrome (AGS) is characterized by the presence of specific IgE‐antibodies to the carbohydrate galactose‐α‐1,3‐galactose (α‐Gal). Sensitization to α‐Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α‐Gal in a high‐risk cohort of forestry employees (FE) in Luxembourg. Methods: Questionnaires and serum samples of FE from Luxembourg (n = 219) were retrospectively analyzed. α‐Gal specific IgE was quantified by ImmunoCAP, α‐Gal specific IgG and subclasses IgG1–4 were determined by ELISA. Additionally, sera from population‐based controls (n = 150) and two groups of food‐allergic patients, patients with AGS (n = 45) and fish‐allergic patients (n = 22) were assessed for IgG antibody responses to α‐Gal and cod extract. Results: Twenty‐one percent of FE was sensitized to α‐Gal (sIgE ≥ 0.1 kUA/L). Both sensitized and non‐sensitized FE exhibited high levels of α‐Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish‐allergic patients was similar to the profile of the controls for which anti‐α‐Gal responses were dominated by IgG2 antibodies. α‐Gal sIgG4 levels were either very low or undetectable in all groups. Conclusion: Our study provides evidence for a continuous stimulation of α‐Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α‐Gal. [ABSTRACT FROM AUTHOR]

The experiment was conducted to study the skin contact damage and stomach injury of direct feeding of alkaline protease. Guinea pigs were taken as animal models, the damage of the skin and stomach caused by alkaline protease were observed with alkaline protease at 0.02, 0.05, 0.10, 0.20 g/mL for skin contact 7 days, and 0, 1, 2, 5 g of alkaline protease were mixed into 100 g feed then fed to healthy guinea pigs for 3 days. The results showed that: ① the continuous contact of alkaline protease with skin 3 days, different concentration groups were caused obvious skin damage and scab, but the damage area (>40%) were not significantly different; when the contact days increased to 7 days, the damage area of 0.10, 0.20 g/mL concentration groups (>90%) were significantly higher than that of 0.02, 0.05 g/mL concentration groups (=79%). ② When the alkaline protease solution of 0.02, 0.10, 0.20 g/mL were continuously exposed to the skin for 2 days, the skin injury score increased significantly; when contact skin for 7 days, the score of each concentration group was > 3, reaching the degree of severe ulceration. ③ Healthy guinea pigs were fed with alkaline protease for 3 days, when the dosage was 1 g/100 g, the guinea pigs' stomach was damaged, but there was no death; when the dosage was 2 g/100 g, the stomach walls of guinea pigs were thinner and the folds were reduced, the mortality rate was 25%; when the dosage was 5 g/100 g, the stomach walls of guinea pigs were extremely thin and the mortality rate reached 75%. The results indicated that: 0.02-0.20 g/mL of alkaline protease enzyme liquid could cause serious damage when it was continuously exposed to the skin for 7 days; the addition of high dose of alkaline protease in the feed could cause stomach injury, and when the additive amount was > 2 g/100 g, it could cause animal death. [ABSTRACT FROM AUTHOR]

PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurons in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved arginine (R2756). Using genome engineering in mice we generated Piezo2 R2756H/R2756H and Piezo2 R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurons isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain-of-function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurons that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurons innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner's corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurons essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurons. Consistently, Piezo2 knock-in mice showed substantial behavioural hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving the voltage-block of PIEZO2 ion channels. Indeed, membrane depolarization caused by multiple noxious stimuli may sensitize nociceptors by relieving voltage-block of PIEZO2 channels. [ABSTRACT FROM AUTHOR]

Large-scale genome-wide association analyses have identified loci of migraine risk that encode inflammation-related genes. Other lines of evidence in humans have further implicated immune dysregulation in migraine, including measurements of peripheral proinflammatory factors and neuroimaging studies. Studies in rodents point to immune dysregulation along the trigeminovascular pathway as a major contributor to migraine's pathophysiology. Reciprocal modulation between the immune cells and the meningeal afferent neurons regulates peripheral and central sensitization, leading to persistent headache and its chronification. Microglia–neuron interactions in the trigeminocervical complex may play an important role in the transition from episodic to chronic migraine. Emerging evidence suggests that regulatory T cells participate in the resolution of migraine headaches. Targeting regulatory T cells may restore the balance between immune activation and suppression to reverse chronic headaches. Migraine is highly prevalent and debilitating. The persistent headaches in this condition are thought to arise from the activation and sensitization of the trigeminovascular pathway. Both clinical and animal model studies have suggested that neuroimmune interactions contribute to the pathophysiology of migraine headache. In this review, we first summarize the findings from human studies implicating the dysregulation of the immune system in migraine, including genetic analyses, measurement of circulatory factors, and neuroimaging data. We next discuss recent advances from rodent studies aimed at elucidating the neuroimmune interactions that manifest at various levels of the trigeminovascular pathway and lead to the recruitment of innate and adaptive immune cells as well as immunocompetent glial cells. These cells reciprocally modulate neuronal activity via multiple pro- and anti-inflammatory mediators, thereby regulating peripheral and central sensitization. Throughout the discussions, we highlight the potential clinical and translational implications of the findings. [ABSTRACT FROM AUTHOR]

Introduction: Poly(ADP-ribose) polymerase 1 (PARP1) inhibition has become a major target in anticancer therapy. While PARP inhibitors (PARPi) are approved for homologous recombination (HR) deficient cancers, therapeutic resistance is a challenge and PARPi are now being investigated in cancers lacking HR deficiencies. This creates a need to develop molecular and imaging biomarkers of PARPi response to improve patient selection and circumvent therapeutic resistance. Areas covered: PubMed and clinicaltrials.gov were queried for studies on PARPi resistance and imaging. This review summarizes established and emerging resistance mechanisms to PARPi, and the current state of imaging and theragnostic probes for PARPi, including fluorescently labeled and radiolabeled probes. Expert opinion: While progress has been made in understanding PARPi therapeutic resistance, clinical evidence remains lacking and relatively little is known regarding PARPi response outside of HR deficiencies. Continued research will clarify the importance of known biomarkers and resistance mechanisms in patient cohorts and the broader utility of PARPi. Progress has also been made in PARPi imaging, particularly with radiolabeled probes, and both imaging and theragnostic probes have now reached clinical validation. Reducing abdominal background signal from probe clearance will broaden their applicability, and improvements to molecular synthesis and radiation delivery will increase their utility. [ABSTRACT FROM AUTHOR]

Quartz plays a crucial role in retrospective dosimetry and dating inquiries in Quaternary Science. The success of thermally and optically stimulated luminescence (TL, OSL) methods depends on the signal repeatability and the signal intensity of quartz grains. Among numerous crystals investigated in the last 20 years, few pieces collected from pegmatitic deposits located near the Solonópole municipality (Ceará State) have shown a notable brightness after being sensitized with a method combining high dose γ radiation and moderate heat treatments. To examine this trend, this paper reviews TL and OSL records measured in six single crystals with different sensitivities by means of different equipment setups and a wide range of γ and β radiation doses. TL emission spectra and trace-element analyses are shown and used to further discuss the complex problem involving electron traps, luminescence centers, and impurity-related point defects into the lattice of quartz. Electron–hole transferring in association with Li+ motion through trapping and recombination centers related to Ge and Al impurities appear to be the basis for a model to explain the brightness of Solonópole samples. This study shows the importance of adopting samples in the single crystal form to further investigate TL and OSL signal properties in quartz. [ABSTRACT FROM AUTHOR]

The sensitization behavior of the welding heat affected zone (HAZ) in austenitic stainless steels (SSs) was investigated through simulated thermal cycles emulating actual multi-pass welding processes using the Gleeble simulator. The tests were performed with austenitic SSs, considering carbon contents, heat input, and distance from the fusion line to determine the thermal cycle conditions of the HAZ. Higher carbon content led to increased sensitization (degree of sensitization, DOS) values, while the influence of the thermal cycle in the final weld pass was that even though it was rapidly heated to over 1000 °C and cooled at a rapid rate, the DOS value decreased due to partial carbide dissolution and chromium diffusion. Therefore, effective management of the final thermal cycle in the HAZ contributes to improved intergranular stress corrosion cracking resistance. Even with prolonged exposure of the HAZ to the sensitization region, the discovery that corrosion resistance improves when the final heating cycle reaches 1000 °C underscores the importance of HAZ heat cycle management and provides valuable insights for materials engineering and industrial applications. [ABSTRACT FROM AUTHOR]

The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as a "pain switch" through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the sensitization of TRPV1 channels, which modulates sensory transmission from primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced peripheral neuropathy (CIPN), TRPV1 is implicated in neuropathic pain mechanisms due to its interaction with ion channels, neurotransmitter signaling, and oxidative stress. Sensitization of TRPV1 in dorsal root ganglion neurons contributes to CIPN development, and inhibition of TRPV1 channels can reduce chemotherapy-induced mechanical hypersensitivity. In diabetic peripheral neuropathy (DPN), TRPV1 is involved in pain modulation through pathways including reactive oxygen species and cytokine production. TRPV1's interaction with TRPA1 channels further influences chronic pain onset and progression. Therapeutically, capsaicin, a TRPV1 agonist, can induce analgesia through receptor desensitization, while TRPV1 antagonists and siRNA targeting TRPV1 show promise in preclinical studies. Cannabinoid modulation of TRPV1 provides another potential pathway for alleviating neuropathic pain. This review summarizes recent preclinical research on TRPV1 in association with peripheral NeuP. [ABSTRACT FROM AUTHOR]

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Summary The prevalence of asthma, rhinitis, and food allergies has increased dramatically over the last few decades. This increase originally started in western countries, but is now also evident in many other regions of the world. Given the fact that the increase is so quick, the noted increase cannot be linked to a genetic effect, and many environmental factors have been identified that are associated with increased or reduced prevalence of allergies, like changing dietary habits, increased urbanization, pollution, exposure to microorganisms and LPS, and the farming environment and raw milk consumption. Although the key role of allergen‐specific IgE in allergies is well known, the role of allergen‐specific IgG and IgA antibodies is less well defined. This review will provide an overview of the functions of allergen‐specific IgE in allergy, the role of allergen‐specific antibodies (IgG (4) and IgA) in allergen immunotherapy (AIT), the possibility to use allergen‐specific antibodies for treatment of ongoing allergies, and the potential role of allergen‐specific antibodies in tolerance induction to allergens in a preventive setting. In the last, more speculative, section we will present novel hypotheses on the potential role of allergen‐specific non‐IgE antibodies in allergies by directing antigen presentation, Th2 development, and innate immune training. [ABSTRACT FROM AUTHOR]

Under conditions of repeated exposure to ethanol, a sensitized locomotor stimulant response develops in some strains of mice. It has been hypothesized that the sensitized response is a consequence of tolerance development to the sedative/incoordinating effects of ethanol. Conversely, ethanol-induced sensitization and tolerance may be independent effects of repeated ethanol exposure. A published study in C57BL/6J by DBA/2J recombinant inbred strains concluded that the two phenomena are not genetically related and thus perhaps mechanistically distinct. To extend evaluation beyond the genetic variance found in C57BL/6J and DBA/2J mice and examine phenotypic associations, we simultaneously measured ethanol-induced sensitization and tolerance in a genetically diverse panel of 15 standard inbred mouse strains and a genetically heterogeneous stock that was produced by the intercrossing of eight inbred mouse strains. Changes in activity counts and ataxia ratio across repeated ethanol treatments indexed sensitization and tolerance, respectively. Photocell beam breaks provided the measure of activity, and foot slip errors corrected for activity in a grid test provided a measure of coordination. The results were strain and individual dependent. The genetic correlation between magnitude of sensitization and tolerance was not significant in the panel of inbred strains, but when individual data were correlated, without regard to strain, there was a significant correlation. This relationship was also significant in the genetically heterogeneous population of mice. However, magnitude of tolerance explained only 10% of the variance in sensitization among individuals of the inbred strain population, whereas it explained 44% of the variance among individuals of the eight-strain cross. When repeated exposures to ethanol were disassociated from the test apparatus, this relationship in the eight-strain cross disappeared. Furthermore, days to peak sensitization and tolerance across days did not perfectly mirror each other. Overall, our data do not support shared genetic mechanisms in sensitization and tolerance development but suggest a partial relationship among individuals that could be related to drug-environment associations. [ABSTRACT FROM AUTHOR]

Introduction: Multiple antigen environmental sources have been identified as possible causes of allergies, but few studies have evaluated changes in the sensitization profiles over time. The aim of this study was to evaluate the changes in IgE sensitization and exposure to dust mites, cats, dogs, and cockroaches over a 10-year period. Methods: During a period of 10 years among patients with asthma, rhinitis and/or atopic dermatitis, we evaluated the annual frequency of atopy to Dermatophagoides farinae, Dermatophagoides pteronyssinus, Blomia tropicalis, Canis familiaris, Felis domesticus and cockroaches (Periplaneta americana and Blatella germanica). Exposure to sources was also assessed using questionnaires (Pets) or direct counts (House dust mites and cockroaches). The association between some risk factors and the prevalence of atopy was explored. Results: A total of 6,000 records were included. Among the patients, 82% had IgE sensitization to at least one of the six allergenic sources. Sensitization to Dermatophagoides spp. was the most frequent (>78%). Exposure and sensitization in the first decade of life to Dermatophagoides spp. seem to determine the molecular spreading to other allergenic sources. Exposure to Blomia tropical increases significantly over time (year 2015; 38% vs. year 2022; 51%, p 0.03). Exposure to dogs was higher than with cats but association between atopy and exposure was stronger with cats (OR 27.4, 95% CI: 22.3–33.6, p < 0.01). Conclusion: Exposure and sensitization in the first decade of life to Dermatophagoides spp. determine the molecular spreading of IgE antibodies to other allergenic sources. Household exposure to dogs and cats seems to be important for the subsequent development of atopy. Sensitization to B. tropicalis and cockroach appears to be mostly from cross-reactivity rather than direct exposure. [ABSTRACT FROM AUTHOR]

Background/Objectives: To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). Methods: A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. Results: The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R2 = 0.642; p = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R2 = 0.827; p = 0.001) and relative CPM (R2 = 0.882; p < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R2 = 0.728; p = 0.02). Conclusions: This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: While a specific number and type of antigens are recognized to detect perennial inhalant allergies, the optimal number and combination of allergens to reliably identify seasonal allergic sensitization is unclear due to limited national data. This study analyzed aeroallergen testing data from a large US clinical reference laboratory to provide guidance for optimizing seasonal allergen test selection. Methods: The 2019 serum IgE tests for seasonal inhalant allergens were identified from the Quest Diagnostics database. Patients with results for at least 1 of 31 seasonal allergens across 4 allergen classes (11 trees, 7 weeds, 5 grasses, and 8 molds) were analyzed. A step-by-step conditional approach was employed to determine the minimum number and species of allergens needed to identify at least 98% of sensitized patients for each class. Results: Of 88,042 patients tested for ≥1 seasonal allergen, 1.5%, 1.8%, 1.3%, and 1.6% were tested for all trees, weeds, grasses, and molds, respectively. Of those tested for all allergens within a class, 40.4%, 38.6%, 29.5%, and 21.2% were sensitized to at least one tree, weed, grass, or mold allergen, respectively. Identification of ≥98% of sensitized patients within a class required 8 allergens for trees (mountain cedar, maple box elder, walnut, white ash, elm, birch, cottonwood, and hickory/pecan), 5 for weeds (common ragweed short, rough pigweed, English plantain, lamb's quarters/goosefoot, and Russian thistle), 3 for grasses (June/Kentucky blue grass, Johnson grass, and Bermuda grass), and 7 for molds (Alternaria alternata, Aspergillus fumigatus, Mucor racemosus, Epicoccum purpurascens, Penicillium notatum, Helminthosporium halodes, and Fusarium moniliforme). Conclusion: A minimum of 23 antigens is required to optimally detect sensitization to four classes of seasonal allergens (i.e., ≥98% identification). The addition of these allergens to unique perennial allergens (cat, dog, mouse, cockroach, and 2 dust mite species) results in a comprehensive elucidation of inhalant allergen sensitization. This knowledge provides a pivotal guide for clinical laboratories as they construct allergen panels to optimize diagnostic yield. [ABSTRACT FROM AUTHOR]

Large number of sensitizers and protectors of cells, tissues, organs and organisms are being discussed in this review. Attention is paid to metals, nanoparticles or organic compounds as modifiers. They can modify the radiation sensitivity by 20–60%. In most cases, sensitization is caused by an increase in DNA damage or a decrease in the repair of radiation damage. The protection can be caused in many cases by repair of damaged DNA molecules, proteins or enzymes, or by reducing the ROS concentration. The most current research tasks in this area are formulated. A new quantitative and reproducible method of evaluating modifiers is discussed. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the sensitization rate of different aeroallergens in children of different age, sex, and disease groups, describe the changing trend of different aeroallergens in different ages, and analyze the sensitization risk factors for asthma. Methods: Children (<18 years old) with suspected atopic diseases who visited the Department of Allergy of Children's Hospital Affiliated to Capital Institute of Pediatrics and underwent a skin prick test (SPT) were retrospectively enrolled from January 2019 to November 2021. Results: A total of 5465 patients (3514 boys, 1951 girls; mean age, 7 ± 3 years) were enrolled. Of them, 3703 patients (67.8%) were sensitized to at least one aeroallergen. Before 4 years of age, mold was the most prevalent aeroallergen (103/380 [27.1%]), whereas after 4 years of age, weed pollen was the most prevalent aeroallergen. After 6 years of age, tree pollen became the second most prevalent aeroallergen. After 12 years of age, the sensitization rate of indoor aeroallergens was lower than that of outdoor aeroallergens. Logistic regression showed that sensitization to mold (odds ratio [OR]:1.4, 95% confidence interval (CI): 1.2–1.7, p < 0.001), animal dander (OR: 1.6, 95% CI: 1.4–1.9, p < 0.001), and polysensitization (OR: 1.4, 95% CI: 1.0–1.8, p = 0.038) were potential sensitization risk factors for asthma. Conclusions: Mold is an important allergen in early life. Different kinds of allergens affect different age groups. Patients who are sensitized to mold or animal dander or experience polysensitization should be carefully monitored for asthma risk. [ABSTRACT FROM AUTHOR]

Introduction: The growing presence of allergens in materials and scarce data on allergic contact dermatitis in children has increased our need to refine its diagnosis in this population. We aimed to analyze children's specific responsivity to highly reactive subcomponents of Fragrance mix I, Fragrance mix II, and Textile dye mix from the European baseline series. Methods: We retrospectively analyzed patch test records of children aged 2 to 18 who underwent patch testing with the European baseline series between 2014 and 2022 in Israel. Results: A total of 367 children were included in the study. In all, 160 children had positive results; 43 patients reacted to one of the mixes, and 20 performed further testing. Eleven of them completed the extended series at the exact same times as the regular European series, which benefited children. Farnesol was the most reactive compound (30.8%). Conclusions: Performing the extended European series provides a more accurate and time‐efficient allergic contact dermatitis diagnosis. Farnesol reactivity appears prominent in children and may justify tighter product regulations. [ABSTRACT FROM AUTHOR]

Abstract Integrating immunotherapy with natural compounds holds promise in enhancing the immune system’s ability to eliminate cancer cells. Cordyceps militaris, a traditional Chinese medicine, emerges as a promising candidate in this regard. This study investigates the effects of cordycepin and C. militaris ethanolic extract (Cm-EE) on sensitizing cancer cells and regulating immune responses against breast cancer (BC) and hepatocellular carcinoma (HCC) cells. Cordycepin, pentostatin and adenosine were identified in Cm-EE. Cordycepin treatment decreased HLA-ABC-positive cells in pre-treated cancer cells, while Cm-EE increased NKG2D ligand and death receptor expression. Additionally, cordycepin enhanced NKG2D receptor and death ligand expression on CD3-negative effector immune cells, particularly on natural killer (NK) cells, while Cm-EE pre-treatment stimulated IL-2, IL-6, and IL-10 production. Co-culturing cancer cells with effector immune cells during cordycepin or Cm-EE incubation resulted in elevated cancer cell death. These findings highlight the potential of cordycepin and Cm-EE in improving the efficacy of cancer immunotherapy for BC and HCC.

Objective: to identify the frequency and etiology of latent sensitization among frequently ill preschool children living in Rostov-on-Don.Materials and methods: 40 preschool-age children (5.3±1.2 years old) who are under medical supervision for frequent respiratory diseases of a protracted nature were examined. According to the nature of the clinical course, the following subgroups were identified: 1st subgroup — frequently ill children with recurrent respiratory tract pathology: adenoiditis, bronchoobstructive syndrome (n=19), 2nd subgroup — frequently ill children with different duration of episodes of acute respiratory diseases: from 3 to 5 days and from 5 to 10 days. The mandatory criterion for inclusion in the group was the absence of hereditary burden due to allergic pathology. All patients underwent an allergological examination, including the determination with the help of an automatic immunochemiluminescent analyzer (Immuno CAP 100 Phadia AB, Switzerland) of specific blood IgE to the antigens of Timothy's meadow, rPh1 p1, Phl p 5; antigens of Altenaria alternata, rAlt a1; antigens of ragweed, nAmb a1; to the antigens of wormwood nArt v1.Results: sensitization to the main allergens that are causally significant for the region is formed in 33–74% of cases in frequently ill preschool children living in Rostov-on-Don. The main causally significant allergen, sensitization to which is diagnosed in most of the subjects, is the major fraction of Ragweed Ragweed (nAmb a1). Sensitization to the major fraction of the common Wormwood allergen (nArt v1) is not diagnosed in a monovariant, but always accompanies hypersensitivity to high Ragweed ragweed.Conclusions: the presence of concomitant pathology of the respiratory tract in the form of adenoiditis, bronchoobstructive syndrome, as well as a long (more than 5 days) course of frequently recurrent acute respiratory diseases is a factor indicating a high probability of latent sensitization in frequently ill preschool children, which is formed in 33-74% of cases. It is recommended that frequently ill children with symptoms of recurrent respiratory tract pathology perform allergodiagnostics with the identification of specific IgE to the main causally significant allergens for the region.

Through-thickness corrosion homogeneity of stabilized AA5083 alloy thick plate was investigated. For the as-received stabilized plates, no differences in corrosion behavior are evident in the specimens from different sampling positions along the thickness direction. However, in the plates after sensitization, the specimen from the surface position (T/10, SP) exhibits the highest degree of sensitization (DoS) and stress corrosion cracking (SCC) susceptibility, indicating the through-thickness corrosion inhomogeneity. Compared with interlayer position (3T/10, IP) and center position (T/2, CP), the higher grain stored energy and richer high angle grain boundaries (HAGBs) in SP specimens promote the formation of β phases (Al3Mg2) during the sensitization process. It results in a high coverage of β phases in the SP specimen and therefore induces severe corrosion.

Introduction: The occurrence of medication errors in hospital settings presents considerable public health challenges, as they significantly affect patient morbidity and mortality, especially with an increasing frequency in critical care units. Material and methods: A prospective before-and-after study conducted in Critical Care Unit 3 at Alexandria Main University Hospital involved 1440 observations of medication errors in 16-bed units over three months, encompassing 181 patients using a checklist. After implementing a sensitization program, a follow-up study was conducted with 1472 observations involving 185 patients over another three months. The comprehensive study focuses on the impact of the sensitization program on medication errors and its reporting, employing a prospective before-after design. Results: No statistically significant difference in mortality was observed between Control and Postintervention groups (p = 0.258). Prescription errors accounted for 52.0%, transcription errors 19.2%, dispensing errors 1.2%, preparation errors 13.9%, and administration errors 13.6% of total medication errors. In the Control group, 38.7% experienced at least one medical error, compared to 21.6% in the Postintervention group (p < 0.001). There were 396 medication errors (27.5% of observations) in the Control group versus 250 errors (17.0% of observations) in the Postintervention group (p < 0.001). Errors reporting increased from 3.8% to 30% (p < 0.001). Conclusions: The non-technological sensitization program effectively reduced medication errors in our resource-limited unit and improved error reporting. [ABSTRACT FROM AUTHOR]

Abstract Background Skin prick tests (SPTs), or intraepidermal tests, are often the first diagnostic approach for people with a suspected allergy. Together with the clinical history, SPTs allow doctors to draw conclusions on allergies based on the sensitization pattern. The purpose of this study is to investigate the potential cost consequences that would accrue to a Swiss University hospital after the adoption of computer vision-based SPTs. Methods We conducted a cost-consequence analysis from a hospital’s perspective to evaluate the potential cost consequences of using a computer vision-based system to read SPT results. The patient population consisted of individuals who were referred to the allergology department of one of the five university hospitals in Switzerland, Inselspital, whose allergology department averages 100 SPTs a week. We developed an early cost-consequence model comparing two SPT techniques; computer vision-based SPTs conducted with the aid of Nexkin DSPT and standard fully manual SPTs. Probabilistic sensitivity analysis and additional univariate sensitivity analyses were used to account for uncertainty. Results The difference in average cost between the two alternatives from a hospital’s perspective was estimated to be CHF 7 per SPT, in favour of the computer vison-based SPTs. Monte Carlo probabilistic simulation also indicated that SPTs conducted using the computer vision-based system were cost saving compared to standard fully manual SPTs. Sensitivity analyses additionally demonstrated the robustness of the base case result subject to plausible changes in all the input parameters, with parameters representing the costs associated with both SPT techniques having the largest influence on the incremental cost. However, higher sensitization prevalence rates seemed to favour the more accurate standard fully manual SPTs. Conclusion Against the backdrop of rising healthcare costs especially in Switzerland, using computer-aided or (semi) automated diagnostic systems could play an important role in healthcare cost containment efforts. However, results should be taken with caution because of the uncertainty associated with the early nature of our analysis and the specific Swiss context adopted in this study.

Abstract Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future. Graphical Abstract

The global trend of incorporating students with disabilities into mainstream education is on the rise, a phenomenon observed in countries like Macedonia and Bosnia and Herzegovina. However, the attitudes of parents with typically developing children play a pivotal role in shaping the educational journey of students with special needs within regular school systems. This study aims to delve into the level of sensitization among parents of typically developing students concerning their peers with diverse developmental disabilities in Macedonia and Bosnia and Herzegovina. Data for this investigation were collected through a survey comprising 10 questions, each offering 3/4 possible responses. The sample size includes 90 parents of typically developing students attending regular schools across North Macedonia and Bosnia and Herzegovina. Thematic analysis of survey results unveils challenges and barriers in the inclusive education process, shedding light on parental sensitization. This exploration identifies specific issues and proposes potential solutions to enhance the inclusivity of the education system. The identified issues emphasize the necessity for targeted interventions and proactive measures to raise awareness among parents, fostering a more supportive and inclusive educational environment. By suggesting plausible solutions, this study contributes to the ongoing discourse on inclusive education, serving as a foundation for further research and practical initiatives.

Background: This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies. Methods: Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible. Results: Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years. Conclusions: Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.

Background: Skin prick tests (SPTs), or intraepidermal tests, are often the first diagnostic approach for people with a suspected allergy. Together with the clinical history, SPTs allow doctors to draw conclusions on allergies based on the sensitization pattern. The purpose of this study is to investigate the potential cost consequences that would accrue to a Swiss University hospital after the adoption of computer vision-based SPTs. Methods: We conducted a cost-consequence analysis from a hospital's perspective to evaluate the potential cost consequences of using a computer vision-based system to read SPT results. The patient population consisted of individuals who were referred to the allergology department of one of the five university hospitals in Switzerland, Inselspital, whose allergology department averages 100 SPTs a week. We developed an early cost-consequence model comparing two SPT techniques; computer vision-based SPTs conducted with the aid of Nexkin DSPT and standard fully manual SPTs. Probabilistic sensitivity analysis and additional univariate sensitivity analyses were used to account for uncertainty. Results: The difference in average cost between the two alternatives from a hospital's perspective was estimated to be CHF 7 per SPT, in favour of the computer vison-based SPTs. Monte Carlo probabilistic simulation also indicated that SPTs conducted using the computer vision-based system were cost saving compared to standard fully manual SPTs. Sensitivity analyses additionally demonstrated the robustness of the base case result subject to plausible changes in all the input parameters, with parameters representing the costs associated with both SPT techniques having the largest influence on the incremental cost. However, higher sensitization prevalence rates seemed to favour the more accurate standard fully manual SPTs. Conclusion: Against the backdrop of rising healthcare costs especially in Switzerland, using computer-aided or (semi) automated diagnostic systems could play an important role in healthcare cost containment efforts. However, results should be taken with caution because of the uncertainty associated with the early nature of our analysis and the specific Swiss context adopted in this study. [ABSTRACT FROM AUTHOR]

Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future. Highlights: An abnormal redox microenvironment plays a critical role in the tumorigenesis, development, and drug resistance of cancer. NPs can selectively act as pro-oxidants, inducing cytotoxicity in cancer cells, while also serving as antioxidants and protectors in normal cells for detoxification. NPs play a dual role in increasing the sensitivity and reversing the drug resistance of cancer cells, primarily through pro-oxidant action and, in some cases, through antioxidant action. The heterogeneities in cellular and molecular biology provide the potential basis for the diverse regulation of NPs on the redox state. The advances in novel redox-sensitive materials and clinical applications of NPs offer promising prospects. [ABSTRACT FROM AUTHOR]

Non‐associative learning plays an important role in the biological and cognitive systems and is one of the important pathways for unsupervised learning in biology. The proposed non‐associative learning memristive circuit is composed of a synapse module, a memristive neuron module, and a response boosting module. The circuit can simulate the characteristics of habituation and sensitization, which attenuates the output response when receiving repeated input stimuli and augments the output response when receiving strong input stimuli, and the circuit also has a certain anti‐interference ability. Additionally, the designed circuit is suitable for adaptive replication experiments in visual systems and automatic exposure compensation systems, demonstrating the practicality of the circuit. [ABSTRACT FROM AUTHOR]

Recently, lanthanide‐based 0D metal halides have garnered considerable attention owing to their applications in light–emitting diodes (LEDs), X‐ray imaging, and photodetectors. Among these materials, 0D Cs3TbCl6 (CTC) nanocrystals (NCs) have demonstrated promising performance in X‐ray imaging and light‐emitting diodes. However, a considerable drawback of CTC NCs is their limited absorption coefficient in the UV‐A region (315–380 nm). To address this limitation and enhance the absorption coefficient in the UV‐A region, Ce3+ is incorporated into CTC NCs—advantageous owing to the high absorption coefficient of Ce3+ in the UV‐A region, attributed to—4f‐5d orbital coupling. In addition, Ce3+ ions sensitize the luminescence of CTC NCs and enhance the photoluminescence quantum yield from 75% to 87%. Energy transfer from Ce3+ to Tb3+ is investigated at different dopant ratios. Furthermore, Cs3CeTbCl6 (CCTC) NCs have been utilized in white LED devices. Understanding such competitive energy transfer in lanthanide‐based perovskite‐inspired metal halides will facilitate the development of novel luminescent metal halides for lighting applications. [ABSTRACT FROM AUTHOR]

Shielding gases had considerable significance in welding metal protection from contamination during welding. Welding protection gas is essential in welding joint quality, connected to the arc characteristics and weldment microstructure. Understanding the influence of welding shielding gas in different metal welding processes is extremely important, and many research papers and experiments have been performed. The current study objective is to analyse and summarize shielding gas variations' effects on welding joint bead geometry, dilution percentage, joint soundness, and microstructure by examining the impacts of different protection gas combinations on AISI 304 stainless steel MIG welding. Three AISI 304 weldment samples were welded with MIG technology and 308L filler wire, and three different gas mixtures as protection gas; the dilution percentage for every sample was calculated to evaluate gas mixture influence on heat concentration on welding zone geometry calculation--ferrite percentage and calculated to estimate and predicate the final welding microstructure and texture. An optical microscope and SEM were employed to reveal weldment microstructure, welding porosity, and defects and study their impact on mechanical properties. Vickers microhardness and tensile tests were done to record gas mixture effects on welding zone hardness and strength. Variation in gas mixture effects on weldments' corrosion resistance was recorded using a corrosion test on every welding sample. These research results can be used as guidelines to achieve the required welding quality in practical welding and provide an excellent foundation for understanding and solving shielding gas issues in the metal welding industry and evaluating welding protection gas mixtures' productivity and quality. The heat input of the three samples is equal due to the use of the same voltage, current, and travel speed; for that, we need to profoundly analyse the weldments microstructure and analyse the impacts of variation in microstructure, which resulted from protection gas mixture effects on the cooling rate on weldments mechanical properties. It fits with the requirements of design criteria. [ABSTRACT FROM AUTHOR]

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen‐specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell‐mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen‐based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head‐to‐head comparative paediatric studies are scarce. Additionally, there are fewer placebo‐controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well‐designed studies. [ABSTRACT FROM AUTHOR]

Background: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body. Methods: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae). Results: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group. Conclusions: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine. [ABSTRACT FROM AUTHOR]

Background: Most studies investigating the prevalence of hand eczema (HE) in professional cleaners use self‐reported questionnaire‐based data. However, no validation studies of self‐reporting of HE among professional cleaners have previously been conducted. Objectives: To investigate (1) the point prevalence of self‐reported HE, (2) the point prevalence of HE estimated by physical examination of the hands and (3) the sensitivity and specificity of self‐reporting of HE compared with the diagnosis based on physical examination among professional cleaners. Methods: Professional cleaners at three different hospitals in Region Zealand were invited to fill out a questionnaire. The point prevalence of self‐reported HE was estimated based on questions from the Nordic Occupational Skin Questionnaire. After completing the questionnaire, each cleaner underwent a physical examination of the hands by a dermatologist on the same day. Results: In total, 234 cleaners were invited to participate in the study, and 224 (response rate = 96.0%) agreed to take part. Based on the self‐reported questionnaires, 5.3% (n = 12) of the cleaners had current HE. Based on an examination by a physician, 19.2% (n = 43) of the cleaners had current HE. The sensitivity of self‐reported HE was found to be 28.0%, while the specificity was found to be 100.0%. The positive predictive value was found to be 100.0%, while the negative predictive value was 85.0%. Conclusion: The true point prevalence of HE among professional cleaners is underestimated when based on self‐reporting. [ABSTRACT FROM AUTHOR]

Background: Due to an increasing occupational usage of isothiazolinone (IT)‐containing preservatives, and their potential to cause skin sensitization and allergic contact dermatitis, that is, chronic disease, there is a need for more knowledge on how highly exposed workers are affected. Objectives: The overall objective was to explore dermatological symptoms of potentially long‐lasting or chronic character in Swedish painters. Methods: Building painters from western and southern Sweden were initially invited to perform a questionnaire on occurrence of skin symptoms. Participants with affirmative responses, and the right inclusion criteria, were further invited to patch testing with four different ITs: benzisothiazolinone (BIT), methylisothiazolinone, methylchloroisothiazolinone and octylisothiazolinone. Results: There was a tendency towards higher occurrence of positive patch test reactions among the painters compared with occupationally unexposed registry patients; however, not statistically significant differences. BIT was the substance most frequently causing positive test results in both groups. The occurrence of adult‐onset eczema was higher in painters than in the control group of electricians, and just shy of statistical significance concerning any of several skin locations (face/legs/arms/hands). Conclusion: Building painters present with positive patch test reactions to common paint preservatives (ITs), and they report adult‐onset eczema more often than do less occupationally exposed groups. [ABSTRACT FROM AUTHOR]

Repeated cocaine use produces adaptations in brain function that contribute to long‐lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity‐regulated cytoskeleton‐associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)—a brain region linked to CUD‐related behavior. We show here that repeated, non‐contingent cocaine administration in global Arc KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience‐dependent sensitization of conditioned place preference (CPP). In contrast to the global Arc KO mice, viral‐mediated reduction of Arc in the adult male, but not female, NAc (shArcNAc) reduced both CPP and cocaine‐induced locomotor activity, but without altering basal miniature or evoked glutamatergic synaptic transmission. Interestingly, cell type‐specific knockdown of Arc in D1 dopamine receptor‐expressing NAc neurons reduced cocaine‐induced locomotor sensitization, but not cocaine CPP; whereas, Arc knockdown in D2 dopamine receptor‐expressing NAc neurons reduced cocaine CPP, but not cocaine‐induced locomotion. Taken together, our findings reveal that global, developmental loss of Arc produces hypersensitized cocaine responses; however, these effects cannot be explained by Arc's function in the adult mouse NAc since Arc is required in a cell type‐ and sex‐specific manner to support cocaine‐context associations and locomotor responses. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss‐of‐function mutations on the natural history of egg sensitization lacks consensus among studies.To evaluate the association between the natural course of egg sensitization and FLG mutations.We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid‐school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white‐specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns.Three similar patterns of egg sensitization (persistent, early‐onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four‐fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2–16.0), p = .03 in CHIBA; 4.3 (1.3–14.7), p = .02 in MAAS).FLG loss‐of‐function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship. [ABSTRACT FROM AUTHOR]

Acrylates and methacrylates, though common in a wide variety of products, especially in the dental industry, can cause adverse skin reactions. These compounds, including 2-hydroxyethyl methacrylate, triethylene glycol dimethacrylate, and bisphenol A-glycidyl methacrylate, are strong contact irritants or allergens. Found in dental prostheses, composite resins, dentin bonding materials, and glass ionomers, they pose a higher risk of exposure for dental personnel. Clinically, acrylate allergies manifest as facial rashes, eczema with cracked skin on fingers (pulpitis), nail dystrophy, and periungual dermatitis. Recently, however, the highest frequency of allergic reactions to acrylates has been observed in the beauty industry due to increased use in artificial nails, eyelashes, and hair extensions. This has led to greater sensitization. Acrylates are also used in medical applications such as bone cement for orthopedic endoprostheses, soft contact lenses, hearing aids, histological preparations, and wound dressings, which can also cause allergic reactions. For example, acrylates in surgical glue can cause severe dermatitis, and diabetic medical devices are also potential sources of allergic contact dermatitis. Given the extensive use and prolonged skin contact of products containing acrylates and methacrylates, this review aims to present current knowledge from the literature on reactions to these compounds across different industries. [ABSTRACT FROM AUTHOR]

In modern medical practice, where polyethylene glycol is widely used as a component of various drugs, such as vaccines, chemotherapy drugs, and antibiotics, including vaccines, the issue of allergic reactions to this substance is becoming increasingly important. The purpose of this study is to review and systematise data on various aspects of allergic reactions to polyethylene glycol with the aim of better understanding their pathogenesis, clinical manifestations, diagnostic methods, and possible treatment approaches. The study analysed literature data in modern databases, such as MEDLINE, PubMed, and Scopus, on allergic reactions to polyethylene glycol, using the keywords: "PEG", "polyethylene glycol", "allergy", "side effect". The main aspects of allergy to this substance were highlighted, including mechanisms of development, diagnostic methods, and possible treatment strategies. The analysis found that allergic reactions to polyethylene glycol can manifest in a variety of ways, including anaphylaxis and systemic reactions. A possible role for the immune response has been identified, including the production of IgE and IgM antibodies, complement activation, and accelerated clearance in response to polyethylene glycol, in blood plasma. Data are also provided on how to diagnose an increased risk of an allergic reaction in patients who have previously received drugs with this type of drug transporter and in patients receiving high molecular weight types of polyethylene glycol. The results of this review contribute to a better understanding of allergic reactions to polyethylene glycol and provide information for the development of more effective diagnostic and treatment methods. [ABSTRACT FROM AUTHOR]

Objective: To study the differences in allergen sensitization of parents and their offspring with respiratory allergic diseases. Methods: We included parents and their children who were both diagnosed with allergic asthma and/or allergic rhinitis, between January 2018 and December 2022. Parent-child dyads were evaluated for sensitization to six categories of allergens viz, dust mite, fungus, animal dander, weed pollen, tree pollen and food allergen, by measuring the allergen-specific immunoglobulin E levels (sIgE). Data of gender, age, feeding history, serum total IgE (tIgE), and absolute eosinophil counts (AEC) were collected and analyzed for differences in allergen sensitization of parents and children. Results: Overall, the AEC in children were significantly higher than that of parents. The sensitivity to fungal allergens in children was significantly higher than that in fathers (33.3% vs 6.7%, P = 0.01) as well as mothers (29.3% vs 8.3%, P = 0.03). Sensitization to food allergens was also higher in children compared to fathers (25.4% vs 7.9%, P = 0.01). Fathers with tree pollen allergen sensitivity, and mothers with weed pollen allergen sensitivity had a significantly increased risk (aOR, 95% CI) of having increased sensitivity to these allergens in their offspring; 24.01 (1.08, 53.99; P = 0.04) and 3.27 (1.08, 9.92; P = 0.04), respectively. Conclusion: Children had greater sensitivity for fungal allergens compared to both parents, as well as food allergy compared to fathers. Fathers with tree pollen allergen sensitivity, and mothers with weed pollen allergen sensitivity had an increased risk of having their children sensitive to these types of allergens [ABSTRACT FROM AUTHOR]

Wheat allergy is a major type of food allergy with the potential for life-threatening anaphylactic reactions. Common wheat, Triticum aestivum (hexaploid, AABBDD genome), was developed using tetraploid wheat (AABB genome) and the ancient diploid wheat progenitor (DD genome)-Aegilops tauschii. The potential allergenicity of gluten from ancient diploid wheat is unknown. In this study, using a novel adjuvant-free gluten allergy mouse model, we tested the hypothesis that the glutenin extract from this ancient wheat progenitor will be intrinsically allergenic in this model. The ancient wheat was grown, and wheat berries were used to extract the glutenin for testing. A plant protein-free colony of Balb/c mice was established and used in this study. The intrinsic allergic sensitization potential of the glutenin was determined by measuring IgE response upon transdermal exposure without the use of an adjuvant. Clinical sensitization for eliciting systemic anaphylaxis (SA) was determined by quantifying the hypothermic shock response (HSR) and the mucosal mast cell response (MMCR) upon intraperitoneal injection. Glutenin extract elicited a robust and specific IgE response. Life-threatening SA associated and a significant MMCR were induced by the glutenin challenge. Furthermore, proteomic analysis of the spleen tissue revealed evidence of in vivo Th2 pathway activation. In addition, using a recently published fold-change analysis method, several immune markers positively and negatively associated with SA were identified. These results demonstrate for the first time that the glutenin from the ancient wheat progenitor is intrinsically allergenic, as it has the capacity to elicit clinical sensitization for anaphylaxis via activation of the Th2 pathway in vivo in mice. [ABSTRACT FROM AUTHOR]