DRESS syndrome due to anti-TB drugs: A complex case with successful re-desensitization of group A drugs.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, life-threatening adverse reaction caused by certain medications. Clinical findings usually include rash, fever, lymphadenopathy, and eosinophilia, and in some cases, they may affect major organs. This reaction caused by antituberculosis (TB) medication poses a public health risk due to treatment discontinuation, adherence, or success in cure. We present a 23-year-old female patient who developed DRESS syndrome as a result of group A anti-TB drugs (ATDs), an exceedingly rare occurrence. The patient's medication was successfully retrieved using a re-desensitization protocol.

Adaptive Processing Enabled by Sodium Alginate Based Complementary Memristor for Neuromorphic Sensory System.

Adaptive processing allows sensory systems to autonomically adjust their sensitivity with exposure to a constant sensory stimulus and thus organisms to adapt to environmental variations. Bioinspired electronics with adaptive functions are highly desirable for the development of neuromorphic sensory systems (NSSs). Herein, the functions of desensitization and sensitivity changing with background intensity (i.e., Weber's law), as two fundamental cues of sensory adaptation, are biorealistically demonstrated in an Ag nanowire (NW)-embedded sodium alginate (SA) based complementary memristor. In particular, Weber's law is experimentally emulated in a single complementary memristor. Furthermore, three types of adaptive NSS unit are constructed to realize a multiple perceptual capability that processes the stimuli of illuminance, temperature, and pressure signals. Taking neuromorphic vision as an example, scotopic and photopic adaptation functions are well reproduced for image enhancement against dark and bright backgrounds. Importantly, an NSS system with multisensory integration function is demonstrated by combining light and pressure spikes, where the accuracy of pattern recognition is obviously enhanced relative to that of an individual sense. This work offers a new strategy for developing neuromorphic electronics with adaptive functions and paves the way toward developing a highly efficient NSS.

The Safety and Efficacy of Baked Egg and Milk Dietary Advancement Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Cow's milk and egg allergy affect approximately 1.9% and 0.9% of children, respectively. Dietary advancement therapies (DAT), including milk (ML) and egg (EL) ladders, baked milk (BM-OIT) and baked egg (BE-OIT) oral immunotherapy are potential therapeutic options for these patients. OBJECTIVE: To perform systematic review and meta-analysis of the safety and efficacy of DAT in children with IgE-mediated milk or egg allergy. METHODS: A systematic literature review was conducted, exploring 22 potential outcomes, with meta-analysis performed where >3 studies reported data. The GRADE approach was used to determine the certainty of evidence for each outcome, and the Johanna Briggs Institute tools for determining risk of bias. RESULTS: Twenty-nine studies met inclusion criteria among 9946 titles screened. Tolerance occurred in 69% of EL, 58% of ML, 49% of BE-OIT and 29% of BM-OIT patients. All-severity allergic reactions occurred in 21% of EL, 25% of ML, 20% of BE-OIT and 61% of BM-OIT patients, with epinephrine use in 3% of EL, 2% of ML, and 9% of BM-OIT patients. At-home reactions occurred in 19% of BE-OIT and 10% of BM-OIT patients. Discontinuation occurred in 14% of EL, 17% of ML, 17% of BE-OIT and 20% of BM-OIT patients. Mean time to BE egg and BE-OIT tolerance was 13.25 months (4 studies) and 19.1 months (3 studies). Certainty of evidence was very low, and risk of bias high. Study heterogeneity was high, attributable to multiple factors. CONCLUSIONS: There is very low certainty of evidence supporting DAT safety and efficacy. We cannot conclude DAT accelerates tolerance development.

Desensitization Strategies for Donor-Specific Antibodies in HLA-Mismatched Stem Cell Transplantation Recipients: What We Know and What We Do Not Know.

In human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation settings, donor-specific anti-HLA antibodies (DSAs) can independently lead to graft failure, including both primary graft rejection and primary poor graft function. Although several strategies, such as plasma exchange, intravenous immunoglobulin, rituximab, and bortezomib, have been used for DSA desensitization, the effectiveness of desensitization and transplantation outcomes in some patients remain unsatisfactory. In this review, we summarized recent research on the prevalence of anti-HLA antibodies and the underlying mechanism of DSAs in the pathogenesis of graft failure. We mainly focused on desensitization strategies for DSAs, especially novel methods that are being investigated in the preclinical stage and those with promising outcomes after preliminary clinical application.

Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood-Brain Barrier.

The N-terminal portion of the octapeptide angiotensin II (DRVYIHPF; AngII), a vasopressor peptide that favorably binds to, and activates, AngII type 1 receptor (AT1R), has an important role in maintaining bioactive conformation. It involves all three charged groups, namely (i) the N-terminal amino group cation, (ii) the Asp sidechain anion and (iii) the Arg guanidino cation. Neutralization of any one of these three charged groups results in a substantial reduction (<5%) in bioactivity, implicating a specialized function for this cluster. In contrast, angiotensin A (ARVYIHPF; AngA) has reduced bioactivity at AT1R; however, replacement of Asp in AngII with sarcosine (N-methyl-glycine) not only restores bioactivity but increases the activity of agonist, antagonist, and inverse agonist analogues. A bend produced at the N-terminus by the introduction of the secondary amino acid sarcosine is thought to realign the functional groups that chaperone the C-terminal portion of AngII, allowing transfer of the negative charge originating at the C-terminus to be transferred to the Tyr hydroxyl-forming tyrosinate anion, which is required to activate the receptor and desensitizes the receptor (tachyphylaxis). Peptide (sarilesin) and nonpeptide (sartans) moieties, which are long-acting inverse agonists, appear to desensitize the receptor by a mechanism analogous to tachyphylaxis. Sartans/bisartans were found to bind to alpha adrenergic receptors resulting in structure-dependent desensitization or resensitization. These considerations have provided information on the mechanisms of receptor desensitization/tolerance and insights into possible avenues for treating addiction. In this regard sartans, which appear to cross the blood-brain barrier more readily than bisartans, are the preferred drug candidates.

A Single Centre Experience of Effective Desensitization Strategy for Children with High Anti-HLA Donor-Specific Antibodies Undergoing Haploidentical Hematopoietic Stem Cell Transplantation.

To assess the incidence of anti-HLA donor-specific antibodies and the effectiveness of desensitization strategy in children who underwent haploidentical HSCT at our hospital. A retrospective review, management and outcomes of children with positive anti-HLA DSA who underwent haploidentical HSCT at our hospital from 2020 to 2022. Three patients with Thalassemia major were treated with 2 cycles of pretransplant immune suppression (PTIS) comprising Fludarabine and Dexamethasone in addition to desensitization. Five out of the 26 children who underwent haploidentical HSCT had positive anti-HLA DSA. Post desensitization, three out of the 5 children engrafted with sustained full donor chimerism, 1 patient developed primary graft rejection, while 1 patient died. It is feasible to desensitize children with high anti-HLA donor specific antibodies undergoing haploidentical HSCT to improve outcomes.

Successful osimertinib rechallenge without concomitant corticosteroids after osimertinib-induced pneumonitis.

A 60-year-old woman was diagnosed with cT4N3M1c stage IVB lung adenocarcinoma with epidermal growth factor receptor mutation of exon19 deletion. After one month of treatment with osimertinib, a cough and diffuse ground glass opacities were observed in the bilateral lung field. Based on the clinical course and the exclusion of other etiologies, osimertinib-induced pneumonitis was diagnosed. The shadows resolved after osimertinib was discontinued. However, brain metastasis and leptomeningeal metastasis developed 20 months later; therefore, osimertinib was re-administered without concomitant corticosteroids. The pulmonary lesion and leptomeningeal metastasis were successfully treated without recurrence of drug-induced pneumonitis for eight months.

Eye movement intervention facilitates concurrent perception and memory processing.

A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.

Proline substitutions in the ASIC1 ß11-12 linker slow desensitization.

Desensitization is a prominent feature of nearly all ligand gated ion channels. Acid-sensing ion channels (ASIC) undergo desensitization within hundreds of milliseconds to seconds upon continual extracellular acidification. The ASIC mechanism of desensitization is primarily due to the isomerization or "flipping" of a short linker joining the 11th and 12th beta sheets in the extracellular domain. In the resting and active states this ß11-12 linker adopts an "upward" conformation while in the desensitized conformation the linker assumes a "downward" state. To accommodate this "downward" state, specific peptide bonds within the linker adopt either trans-like or cis-like conformations. Since proline-containing peptide bonds undergo cis-trans isomerization very slowly, we hypothesized that introducing proline residues in the linker may slow or even abolish ASIC desensitization, potentially providing a valuable research tools. Proline substitutions in the chicken ASIC1 ß11-12 linker (L414P and Y416P) slowed desensitization decays approximately 100 to 1000-fold as measured in excised patches. Both L414P and Y416P shifted the steady state desensitization curves to more acidic pHs while activation curves and ion selectivity of these slow-desensitizing currents were largely unaffected. To investigate the functional stoichiometry of desensitization in the trimeric ASIC, we created families of L414P and Y416P concatemers with zero, one, two or three proline substitutions in all possible configurations. Introducing one or two L414P or Y416P mutations only slightly attenuated desensitization, suggesting that conformational changes in the remaining faster wild type subunits were sufficient to desensitize the channel. These data highlight the unusual cis-trans isomerization mechanism of ASIC desensitization and support a model where a single subunit is sufficient to desensitize the entire channel.

Virtual realities, real recoveries: exploring the efficacy of 3MDR therapy for treatment-resistant PTSD.

Exposure-based therapies have shown promise in treating post-traumatic stress disorder (PTSD), but challenges exist in maintaining patient engagement and finding appropriate stimuli for graded exposure. Virtual reality (VR) technology has been used to enhance exposure therapy, but current software lacks customization and some patients remain treatment-resistant. A novel approach called multimodular motion-assisted memory desensitization and reconsolidation (3MDR) has the potential to solve some of the current limitations of VR-assisted exposure therapy. This study examines the efficacy of 3MDR treatment for individuals with treatment-resistant PTSD through a systematic review of relevant literature and clinical studies. Preliminary findings indicate promise for 3MDR in reducing PTSD symptoms, including emotional regulation and moral injury. However, further research with larger samples and controlled studies is needed to understand underlying mechanisms and validate these results. Moreover, this study highlights the importance of health-economic evaluations to assess costs and resource utilization associated with implementing 3MDR treatment in clinical services.

Penicillin Allergy: Mechanisms, Diagnosis, and Management.

Allergy to penicillin can occur via any of the 4 types of Gel-Coombs hypersensitivity reactions, producing distinct clinical histories and physical examination findings. Treatments include penicillin discontinuation, and depending on the type of reaction, epinephrine, antihistamines, and/or glucocorticoids. Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins. Penicillin testing includes skin testing, patch testing, and graded challenge. The selection of the type of testing depends on the clinical setting, equipment availability, and type of hypersensitivity reaction. Desensitization may be used in some cases where treatment with penicillins is essential.

Seminal plasma hypersensitivity: A systematic review of clinical presentation, diagnostics, and management options.

INTRODUCTION: Seminal plasma hypersensitivity (SPH) is a rare and often misdiagnosed condition characterized by local and/or systemic reactions to seminal plasma proteins following exposure to semen. We aimed to summarize key symptomatology, diagnostic features, and management options for SPH. METHODS: The databases PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Review were searched with key words "seminal plasma hypersensitivity" and "seminal fluid allergy" through September 2023. Exclusion criteria included non-English articles, in vitro studies, publication before 1990, duplicates, and articles with no clinical relevance to SPH in women. RESULTS: The search yielded 53 articles for review. Of these, 60.5% described systemic SPH and 39.5% described localized. CONCLUSION: Diagnosis of SPH relies on a thorough patient history and confirmatory skin prick testing. The use of IgE assays is controversial and less accurate for cases of localized SPH. Knowledge of disease immunopathology, systemic versus localized symptom presentation, patient preference, and desire to conceive should guide management options. Artificial insemination has the potential for severe adverse reactions in systemic SPH so necessitates extra procedural precautions. SPH does not appear to impair fertility. Additional research on specific allergens implicated in SPH can aid in the development of more targeted immunotherapy approaches with improved safety and efficacy.

Revisiting Eye Movement Desensitization and Reprocessing Therapy for Post-traumatic Stress Disorder: A Systematic Review and Discussion of the American Psychological Association's 2017 Recommendations.

This literature review evaluates the efficacy and clinical applications of eye movement desensitization and reprocessing (EMDR) therapy for post-traumatic stress disorder (PTSD). The review highlights the effectiveness of EMDR in reducing PTSD symptoms and explores variations in treatment protocols, populations studied, and outcome measures. We conducted systematic searches of multiple databases, supplemented with manual searches and reference list exploration. The inclusion criteria focused on English-language studies published between January 2000 and June 2023, with a specific emphasis on adult psychiatric patients with PTSD receiving EMDR treatment. The review utilized Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for narrative literature reviews. Out of 867 identified studies, 16 met the eligibility criteria. Most studies found that EMDR was superior in relieving PTSD when compared to controls. Eleven of the 16 selected studies demonstrated improvement in PTSD symptoms. An additional three studies noted an improvement in PTSD symptoms when compared to their waitlist control counterparts. One study found EMDR superior in combating depressive symptoms when compared to rapid eye movement desensitization. EMDR therapy is an appropriate treatment for PTSD. Although some studies compared to waitlist controls, and others have a small number of participants, the data supports the use of EMDR for PTSD. Future studies are needed to continue to better understand the mechanism and application in different populations.

Effect of adding systematic desensitization to goal-directed paradigm on risk of falling in patients with stroke: a randomized controlled trial.

Background: Improvement in rehabilitation outcomes for patients suffering from chronic stroke can be attained through systematic desensitization of their fear of falling, which in turn reduces the risk of falling. Purpose: This study aimed to examine the effect of adding systematic desensitization to a goal-directed paradigm on functional performance, balance, risk of falling, and fear of falling among chronic ischemic stroke patients. Methodology: Two equally sized groups, each comprising 40 stroke patients of both sexes, were randomly divided. For 8 weeks, Group A received three sessions per week of combined treatment consisting of systematic desensitization and a goal-directed paradigm, while Group B received only the goal-directed paradigm. The Timed Up and Go (TUG) test and Dynamic Gait Index (DGI) were used to assess function performance; the Berg Balance Scale (BBS) and the Biodex Fall Risk Index (FRI) were used to evaluate balance; and the 16-item Fall Efficacy Scale-International (FES-I) was used to evaluate fear of falling. At baseline and after the treatment, all measurements were obtained. Results: Both groups (A and B) revealed a substantial increase in functional performance through a decrease in TUG scores and an increase in DGI. Additionally, there was a decrease in the risk of falling through an increase in the BBS scores and a decrease in the FRI. Furthermore, there was a decrease in the fear of falling, as measured using the FES-I, after treatment, with superior improvement in Group A with a p-value of <0.001. Conclusion: Systematic desensitization combined with a goal-directed paradigm has a superior effect on improving functional performance and reducing the risk of falling and the fear of falling in patients with stroke compared to a goal-directed paradigm alone.

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

Exacerbation of central serous chorioretinopathy during trauma-confronting psychotherapy- a case report.

BACKGROUND: Psychotherapy for post-traumatic stress disorder, in particular trauma-confronting psychotherapy, can be associated with increased stress. However, research on the somatic impact and psychosomatic interactions of these psychological stress reactions is lacking. We report on a 43-year old man whose central serous chorioretinopathy exacerbated upon trauma-confronting psychotherapy. CASE PRESENTATION: We report on a man with pre-diagnosed, asymptomatic central serous chorioretinopathy who underwent inpatient psychosomatic therapy. He disclosed a history of sexual abuse by a family member and consequently showed intrusions, flashbacks, nightmares, avoidance behavior, and hyperarousal. Thus, we diagnosed post-traumatic stress disorder. After a stabilization phase, he underwent trauma-focused psychotherapy including trauma confrontation. In the course of this treatment, acute vision loss with blurred vision and image distortion of his right eye occurred. An ophthalmologic visit confirmed a relapse of a pre-diagnosed central serous chorioretinopathy. The analysis of stress biomarkers showed a decrease in testosterone levels and a noon peak in diurnal cortisol secretion, which is indicative of a stress reaction. CONCLUSION: Central serous chorioretinopathy may exacerbate upon psychotherapeutic treatment. In this case, an exacerbation of chorioretinopathy was observed in direct relation to the therapeutic intervention. Psychotherapists and ophthalmologists should collaborate in the psychotherapeutic treatment of patients with chorioretinopathy. Our case demonstrates the need to consider the possible increased stress levels during psychotherapy and resulting physical side effects, such as exacerbation of an existing condition. It is advisable to adjust the level of generated stress particularly well in the presence of stress-inducible physical diseases. Our case is a good example of the interplay between psychological and physical stress.