Escala de alerta precoce na identificação de pacientes com risco de deterioração clínica / Early warning scale for identifying patients at risk of clinical deterioration / Escala de alerta temprana en la identificación de pacientes con riesgo de deterioro clínico

Objetivo: avaliar pontuação da National Early Warning Score (NEWS) em relação ao tipo de desfecho e perfil dos pacientes da enfermaria clínica médica de um hospital em Teresina, Piauí, Brasil. Método: estudo quantitativo realizado num hospital público, em Teresina, com 150 prontuários de pacientes internados no setor clínica médica de fevereiro de 2022 a dezembro de 2022, a partir de registros demográficos, clínicos e valores da escala na admissão e desfecho. Resultados: houve associação dos valores da escala com a faixa etária (p=0,029), tempo de internação (p=0,023) e tipo de desfecho (p < 0,001). Alto risco clínico prevaleceu entre pacientes do sexo masculino (13%), na faixa etária de 60 a 94 anos (13%), com permanência de 21 a 57 dias (19,2%) e óbito como desfecho (100%). Conclusão: implementação da referida escala evidenciou ser fundamental para prever agravos clínicos e melhorar qualidade da assistência.

Objective: to evaluate the National Early Warning Score (NEWS) in relation to the type of outcome and profile of patients in the medical clinical ward of a hospital in Teresina, Piauí, Brazil. Method: a quantitative study conducted in a public hospital in Teresina, with 150 medical records of patients admitted to the medical clinic sector from February 2022 to December 2022, based on demographic and clinical records and scale values at admission and outcome. Results: there was an association between the scale values and the age group (p=0.029), length of stay (p=0.023) and type of outcome (p < 0.001). High clinical risk prevailed among male patients (13%), aged between 60 and 94 years (13%), with a stay of 21 to 57 days (19.2%), and death as an outcome (100%). Conclusion: implementation of the aforementioned scale proved to be fundamental for predicting clinical problems and improving care quality.

Objetivo: evaluar el puntaje de la National Early Warning Score (NEWS) con respecto al tipo de desenlace y el perfil de los pacientes de la enfermería clínica médica de un hospital en Teresina, Piauí, Brasil. Método: estudio cuantitativo realizado en un hospital público en Teresina, con 150 historiales médicos de pacientes internados en el sector de clínica médica desde febrero de 2022 hasta diciembre de 2022, a partir de registros demográficos, clínicos y valores de la escala en la admisión y desenlace. Resultados: hubo asociación de los valores de la escala con la edad (p=0,029), tiempo de internación (p=0,023) y tipo de desenlace (p < 0,001). El alto riesgo clínico prevaleció entre los pacientes del sexo masculino (13%), en la franja de edad entre 60 y 94 años (13%), con una estancia de 21 a 57 días (19,2%) y fallecimiento como desenlace (100%). Conclusión: la implementación de dicha escala demostró ser fundamental para prever agravios clínicos y mejorar la calidad de la asistencia.

Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

Quantitative proteomics reveals significant variation in host responses of cattle with differing buffalo fly susceptibility.

Background: Control of buffalo flies (Haematobia irritans exigua, BFs) relies mainly on chemical methods; however, resistance to insecticides is widespread in BF populations. Breeding for resistance to BFs represents a possible alternative, but direct phenotyping of animals is laborious and often inaccurate. The availability of reliable diagnostic biomarker(s) to identify low BF carrier cattle would facilitate rapid and accurate selection for genetic improvement. However, limited information is available regarding differences amongst cattle in host responses to BF infestation. Methods: This study investigated the variation in Brangus cattle serum proteomic profiles before (naïve) and after peak BF exposure, in low (LF) and high BF burden (HF) cattle. Cattle were phenotyped for susceptibility based on BF counts on multiple dates using visual and photographic techniques. The relative abundance of serum proteins in cattle before and after exposure to BFs was analysed using sequential window acquisition of all theoretical fragment ion mass spectrometry (SWATH-MS). Results: Exposure to BFs elicited similar responses in HF and LF cattle, with 79 and 70 proteins, respectively, showing significantly different abundances post exposure as compared to their relevant naïve groups. The comparison of serum samples from naïve HF and LF cattle identified 44 significantly differentially abundant (DA) proteins, while 37 significantly DA proteins were identified from the comparison between HF and LF cattle post-exposure to BFs. Proteins with higher abundance in naïve LF cattle were enriched in blood coagulation mechanisms that were sustained after exposure to BFs. Strong immune response mechanisms were also identified in naïve LF cattle, whereas these responses developed in HF cattle only after exposure to BF. High BF cattle also showed active anticoagulation mechanisms in response to BF exposure, including downregulation of coagulation factor IX and upregulation of antithrombin-III, which might facilitate BF feeding. Conclusion: Underlying differences in the abundance of proteins related to blood coagulation and immune response pathways could potentially provide indirect indicators of susceptibility to BF infestation and biomarkers for selecting more BF-resistant cattle.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients.

This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.

Clinicopathological features affecting the efficacy in 131I ablation therapy of papillary thyroid carcinoma with lymph node metastasis.

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131I ablation therapy. Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed. Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group. Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR.

Impact of nutritional support on immunity, nutrition, inflammation, and outcomes in elderly gastric cancer patients after surgery.

BACKGROUND: Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention. Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function, nutritional status, inflammatory response, and clinical outcomes of this special population has not yet been fully verified. AIM: To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer. METHODS: This is a retrospective study, including 60 elderly gastric cancer patients aged 70 years and above, divided into a nutritional support group and a control group. The nutritional support group received full postoperative nutritional support, including individualized meal formulation, and intravenous and parenteral nutrition supplementation, and was regularly evaluated and adjusted by a professional nutrition team. The control group received routine postoperative care. RESULTS: After intervention, the proportion of CD4+ lymphocytes (25.3% ± 3.1% vs 21.8% ± 2.9%, P < 0.05) and the level of immunoglobulin G (12.5 G/L ± 2.3 G/L vs 10.2 G/L ± 1.8 G/L, P < 0.01) were significantly higher in the nutritional support group than in the control group; the changes in body weight (-0.5 kg ± 0.8 kg vs -1.8 kg ± 0.9 kg, P < 0.05) and body mass index (-0.2 ± 0.3 vs -0.7 ± 0.4, P < 0.05) were less significant in the nutritional support group than in the control group; and the level of C-reactive protein (1.2 mg/L ± 0.4 mg/L vs 2.5 mg/L ± 0.6 mg/L, P < 0.01) and WBC count (7.2 × 109/L ± 1.5 × 109/L vs 9.8 × 109/L ± 2.0 × 109/L, P < 0.01) were significantly lower in the nutritional support group than in the control group. In addition, patients in the nutritional support group had a shorter hospital stay (10.3 d ± 2.1 d vs 14.8 d ± 3.6 d, P < 0.05) and lower incidence of infection (15% vs 35%, P < 0.05) in those of the control group. CONCLUSION: The intervention by the nutritional support team has a positive impact on postoperative immune function, nutritional status, inflammatory response, and clinical outcomes in elderly patients with gastric cancer.

NKT cells promote Th1 immune bias to dengue virus that governs long term protective antibody dynamics.

NKT cells are innate-like T cells, recruited to the skin during viral infection, yet their contributions to long-term immune memory to viruses are unclear. We identified granzyme K, a product made by cytotoxic cells including NKT cells, is linked to induction of Th1-associated antibodies during primary dengue virus (DENV) infection in humans. We examined the role of NKT cells in vivo using DENV-infected mice lacking CD1d-dependent (CD1ddep) NKT cells. In CD1d-KO mice, Th1-polarized immunity and infection resolution were impaired, which was dependent on intrinsic NKT cell production of IFN-γ, since it was restored by adoptive transfer of WT but not IFN-γ-KO NKT cells. Furthermore, NKT cell deficiency triggered immune bias, resulting in higher levels of Th2-associated IgG1 than Th1-associated IgG2a, which failed to protect against a homologous DENV re-challenge and promoted antibody-dependent enhanced disease during secondary heterologous infections. Similarly, Th2-immunity, typified by a higher IgG4:IgG3 ratio, was associated with worsened human disease severity during secondary infections. Thus, CD1ddep NKT cells establish Th1 polarity during the early innate response to DENV, which promotes infection resolution, memory formation and long-term protection from secondary homologous and heterologous infections. These observations illustrate how early innate immune responses during primary infections can influence secondary infection outcomes.

The crosstalk between DNA-damage responses and innate immunity.

DNA damage is typically caused during cell growth by DNA replication stress or exposure to endogenous or external toxins. The accumulation of damaged DNA causes genomic instability, which is the root cause of many serious disorders. Multiple cellular organisms utilize sophisticated signaling pathways against DNA damage, collectively known as DNA damage response (DDR) networks. Innate immune responses are activated following cellular abnormalities, including DNA damage. Interestingly, recent studies have indicated that there is an intimate relationship between the DDR network and innate immune responses. Diverse kinds of cytosolic DNA sensors, such as cGAS and STING, recognize damaged DNA and induce signals related to innate immune responses, which link defective DDR to innate immunity. Moreover, DDR components operate in immune signaling pathways to induce IFNs and/or a cascade of inflammatory cytokines via direct interactions with innate immune modulators. Consistently, defective DDR factors exacerbate the innate immune imbalance, resulting in severe diseases, including autoimmune disorders and tumorigenesis. Here, the latest progress in understanding crosstalk between the DDR network and innate immune responses is reviewed. Notably, the dual function of innate immune modulators in the DDR network may provide novel insights into understanding and developing targeted immunotherapies for DNA damage-related diseases, even carcinomas.

Application of blood parameters for the early diagnosis of natural ascending placentitis in pregnant mares.

Placental infection is an important cause of late-term pregnancy loss and neonatal diseases in horses. Detection of changes in blood parameters especially during early placentitis could improve the diagnostic accuracy, treatment decision, and potential outcomes. The objectives of this 2-part study were to identify differences in circulating immunological, inflammatory, and hormonal parameters between mares with natural ascending placentitis and control mares; evaluate each and combination of parameters as predictors of placentitis; and determine how these parameters indicate severity of placentitis. Reproductive examination and blood sampling were prospectively performed on pregnant mares in a natural setting. Study 1 enrolled mares diagnosed with early stage of ascending placentitis based on ultrasonographic findings (n = 12), and gestationally age-matched mares with healthy pregnancies as controls (n = 12). Blood samples were classified as pre-onset (before) and early onset (at the time of ultrasonographic changes) of placentitis. There were no detected statistically significant differences between groups and timepoints in immunological and inflammatory parameters, including peripheral lymphocyte subpopulations, cytokine, and serum amyloid A concentrations. The placentitis group showed a reduced (P = 0.01) DHP/20α-DHP ratio when compared to the control group at the early onset timepoint. Plasma estradiol-17ß concentration <359 pg/mL predicted ascending placentitis with acceptable accuracy (area under the curve, AUC = 0.71). Combined albumin <3.7 g/dL, estradiol-17ß < 499 ng/mL, and DHP <33 ng/mL predicted 100 % of cases of ascending placentitis. In study 2, samples were classified according to the presence and severity of the abnormal ultrasonographic findings as mild (n = 11) and moderate-severe (n = 23), and gestationally age-matched with samples from control mares (n = 34). Mares with moderate-severe ascending placentitis had increased (P = 0.03) plasma 20α-DHP concentration and reduced (P = 0.03) DHP/20α-DHP ratio when compared to control mares. Our results suggest that the early events of ascending placentitis detected by ultrasonographic findings include hormonal alterations of feto-placental metabolism measurable in the mare's circulation, yet without obvious systemic immunological and inflammatory changes. Additional studies are warranted to further assess how hormonal markers and cutoff values could guide decisions for timely therapeutic intervention.

An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge.

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 µg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 µg and 20 µg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

The ATP-driven extractor ATAD1/Msp1 proof-reads protein translocation into mitochondria.

The accumulation of translocation intermediates in the mitochondrial import machinery threatens cellular fitness and is associated with cancer and neurodegeneration. A recent study by Weidberg and colleagues identifies ATAD1 as an ATP-driven extraction machine on the mitochondrial surface that pulls precursors into the cytosol to prevent clogging of mitochondrial import pores.

Treatment response assessment of acute pyelonephritis: A multi-reader DWI-based MRI approach.

PURPOSE: To evaluate the diagnostic accuracy of a structured reporting score (SRS) in treatment response assessment for acute pyelonephritis (APN) using a diffusion-weighted imaging (DWI) -based MRI approach. Additionally, we explored the influence of reader experience on the interpretation of SRS and DWI, including lesion conspicuity and measurements of Apparent Diffusion Coefficient (ADC) maps. METHODS: Follow-up DWI-based MRIs of 36 patients treated for APN between September 2021 and June 2023 were retrospectively reviewed by three readers. Follow-up blood inflammatory markers were used as reference standard. Treatment response was assessed using a structured reporting score (SRS). Each reader assigned a score from 1 to 3 to the "conspicuity" of the residual disease on DWI. Quantitative ADC measurements were compared with the Mann-Whitney U test. Descriptive statistics and Intraclass Correlation Coefficient (ICC) were calculated. RESULTS: The diagnostic accuracy of SRS was 80.6 %, 76.9 %, and 72.2 % for the Reader 1, 2, and 3 respectively. ICC decreased from 0.82 (Reader 1 and 2), to 0.68 when considering all readers. The average conspicuity varied between 2.3 and 2.7. ADC values were significantly higher in complete responders for Reader 1 and 2 (153.5-154.5 vs 107.7-116.2, p < 0.001). The ICC was good (0.89) for Reader 1 and 2 and moderate (0.60) when considering all readers. CONCLUSIONS: Treatment response of pyelonephritis can be accurately assessed by a DWI-based MRI, potentially avoiding unnecessary contrast agent administration and radiation exposure. SRS and DWI analysis showed a good inter-observer agreement but a certain learning curve may be necessary for less expert readers.

Efficiency of Cysticidal Therapy Impacted by the Host's Immune Response in Neurocysticercosis Patients.

Neurocysticercosis (NCC) is a neurological condition caused by the presence of cysts of Taenia solium in the brain, which manifests with a range of clinical symptoms. The severity of NCC and its prognosis following anti-helminth drug (AHD) treatment are closely linked to peripheral and local inflammation. The study aimed to analyse the efficiency of cysticidal therapy impacted by the host's immune response in NCC patients. A total of 104 patients were screened in this study, and blood samples were collected from 30 patients. The follow-up samples within 3 to 6 months of treatment were collected. Patients were categorised as Responder (R) and Non-Responder (NR). Cytokines IL-6, IL-10, IFN-γ and TNF-α were estimated using ELISA kits in PBMC cells. T0 is the time point before the AHD treatment begins, and T1 is between 3 to 6 months after the treatment starts. The responder patients showed significantly lower IL-10 and IL-6 levels in the supernatants at T0 as compared to T1, while in non-responder patients, IL-10 and IL-6 levels were higher at T0 as compared to T1. The IFN-γ and TNF-α levels were found to be higher in the supernatants at T0 as compared to T1 in both the responder and non-responder patients. These observations imply that these cytokines might have an impact on the efficacy of AHD treatment in NCC patients.

IGJ depletion suppresses proliferation, inflammation, and motility of rheumatoid arthritis fibroblast-like synoviocytes via targeting NF-κB pathway.

OBJECTIVE: To investigate the impact of IGJ on the proliferation, inflammation, and motility of rheumatoid arthritis (RA) fibroblast-like synoviocytes and elucidate the underlying mechanism. METHODS: The expression of IGJ RA fibroblast-like synoviocytes was assessed using immunoblot and qPCR. Cell growth was evaluated using CCK-8 and FCM assays. The effects on inflammatory response were determined by ELISA and immunoblot assays. Cell motility was assessed using transwell and immunoblot assays. The mechanism was further confirmed using immunoblot assays. RESULTS: IGJ expression was found to be elevated in fibroid synovial cells of RA. IGJ ablation inhibited the growth of MH7A cells and suppressed the inflammatory response. Knockdown of IGJ also blocked cell motility. Mechanically, the knockdown of IGJ suppressed the NF-κB axis in MH7A cells. CONCLUSION: IGJ suppresses RA in fibroblast-like synoviocytes via NF-κB pathway.

Decellularized Matrices for the Treatment of Tissue Defects: from Matrix Origin to Immunological Mechanisms.

Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-ß/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

miRNA-Targeted Vaccines: A Promising Approach for Viral Attenuation and Immunogenicity Enhancement.

MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells. This property is harnessed to develop live attenuated vaccines that are tissue-specific, enhancing safety and immunogenicity. The review highlights recent advancements in using miRNA-targeted vaccines against viruses like influenza, poliovirus, and tick-borne encephalitis virus, demonstrating their attenuated replication in specific tissues while retaining immunogenicity. We also explored the function of miRNAs in the biology of cancer, highlighting their potential to develop cancer vaccines through targeting miRNAs that are overexpressed in tumor cells. The difficulties in developing miRNA vaccines are also covered in this work, including delivery, stability, off-target effects, and the requirement for individualized cancer treatment plans. We wrap off by discussing the potential of miRNA vaccines and highlighting how they will influence the development of vaccination techniques for cancer and infectious diseases in the future.

Subcellular expression of CD30 in cutaneous mastocytosis-An important factor for targeted treatment.

BACKGROUND: The subcellular distribution of CD30 on mast cells and the presence of eosinophils in cutaneous mastocytosis require further investigation, especially as the cell surface expression of CD30 is critical for the therapeutic response of systemic mastocytosis to brentuximab vedotin. OBJECTIVE: Investigation of 147 biopsy specimens from 143 patients with cutaneous mastocytosis for mast cell density and distribution, frequency of CD30 expression, CD30 staining patterns, and presence and distribution of eosinophils. Correlation with clinical patterns. METHODS: Retrospective multicenter immunohistochemical study of CD30 expression, eosinophils and basic clinical data in cutaneous mastocytosis. RESULTS: CD30 expression was found in all samples (cut-off: ≥1%), whereby the staining was predominantly cytoplasmic in 99% of the samples. Additional membrane staining was detected in 62% of the samples. Surface expression of CD30 was more common in biopsy specimens with a high mast cell burden and in biopsy specimens with a higher CD30 expression rate. Eosinophils were admixed in 58% of the samples. Females and older patients showed a trend of a lower mast cell burden. LIMITATIONS: Retrospective study on formalin-fixed and paraffin-embedded tissue without functional analysis. CONCLUSION: Most cases of cutaneous mastocytosis show cell surface expression of CD30 expression and is, therefore, in principle, accessible for therapy with antibodies against CD30, provided the overall situation of the patient warrants.

STOP1 regulates CCX1-mediated Ca2+ homeostasis for plant adaptation to Ca2+ deprivation.

Calcium (Ca) is essential for plant growth and stress adaptation, yet its availability is often limited in acidic soils, posing a major threat to crop production. Understanding the intricate mechanisms orchestrating plant adaptation to Ca deficiency remains elusive. Here, we show that the Ca deficiency-enhanced nuclear accumulation of the transcription factor SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) in Arabidopsis thaliana confers tolerance to Ca deprivation, with the global transcriptional responses triggered by Ca deprivation largely impaired in the stop1 mutant. Notably, STOP1 activates the Ca deprivation-induced expression of CATION/Ca2+ EXCHANGER 1 (CCX1) by directly binding to its promoter region, which facilitates Ca2+ efflux from endoplasmic reticulum to cytosol to maintain Ca homeostasis. Consequently, the constitutive expression of CCX1 in the stop1 mutant partially rescues the Ca deficiency phenotype by increasing Ca content in the shoots. These findings uncover the pivotal role of the STOP1-CCX1 axis in plant adaptation to low Ca, offering alternative manipulating strategies to improve plant Ca nutrition in acidic soils and extending our understanding of the multifaceted role of STOP1.