bluuebunny/crossref_metadata_2025 huggingface dataset:
Os princípios do “Specula Principum” nas narrativas pedagógicas de Ramon Llull
Authors: Oliveira Fabiana
Published: June 2022

A presente reflexão tem como objetivo discutir as narrativas pedagógicas para a formação política do príncipe, presentes na obra de Ramon Llull. A obra analisada se caracteriza como fonte de formação moral e política, de modo que fazemos referência desta obra aos “Espelhos de Príncipe” (Specula Principum) enquanto narrativas medievais pautadas em uma pedagogia prescritiva e normativa. O bom príncipe, de acordo com Llull, deve ser a imagem de Deus na terra, numa compreensão dicotômica entre o bom e o mau príncipe. O que fará um bom ou mau príncipe serão suas escolhas diante da liberdade que lhe foi concedida e da sua educação.
Trabalho e inserção social: identidade e etnicidade nas frentes de trabalho da hortelã na microrregião de Toledo, Paraná
Authors: Pedersen Voll Francisco André , Schallenberger Erneldo
Published: June 2022

A partir da década de 1950 a microrregião de Toledo/PR foi ocupada por frentes populacionais originarias de várias partes do país, sendo que uma das maiores foi a de trabalhadores vindos de estados ao norte do Paraná. Estas pessoas trabalharam nas lavouras de hortelã durante um período em que os derivados desta planta, sobretudo o mentol, alcançaram um preço elevado no mercado internacional. Os “sujeitos da hortelã” tiveram de se inserir em um espaço já ocupado por outros grupos, fossem colonos vindos do sul do país ou do Estado de São Paulo, e tiveram de encontrar e construir o seu espaço. Apesar de estranhamentos relacionados aos diferentes modos de vida, os sujeitos da hortelã conseguiram os seus espaços de sociabilidade dentro desta região enquanto estiveram inseridos pelo viés socioprodutivo
Papeis de gênero e seus imaginários por Clarice Lispector na imprensa de 1959-1960
Authors: Santos José Carlos dos , Sopelsa Kaona
Published: June 2022

Este artigo discute as representações de gênero em textos editoriais de jornais de autoria de Clarice Lispector, veiculados pela imprensa paulista no período dentre 1959 e 1960, período histórico de ascensão da classe média, de crescimento urbano, trabalhista e de industrialização, que impactou profundamente os papeis sociais de mulheres e homens da época. Este contexto foi o principal fomentador da produção literária de Clarice Lispector. Publicados no Correio da Manhã, os textos tinham como alvo a mulher adulta, sua sensibilidade, sua beleza e seus papeis no espaço social, num imaginário que pendula, entre a sedução e a virtuosidade e a modernidade e o conservadorismo. Uma discussão sobre a identidade feminina, na modernidade.
Hidrografia urbana: desigualdade socioespacial em áreas irregulares em Ponta Grossa, Paraná/Brasil
Authors: Madalozzo Nisiane , Souza Edson Belo Clemente de
Published: June 2022

O presente artigo visa analisar a ocupação irregular às margens do córrego do Lajeadinho, em Ponta Grossa – PR, como estudo de caso para uma situação identificada de forma recorrente em leitos de rios urbanos na cidade de Ponta Grossa – PR. A hidrografia urbana pode ser considerada um importante elemento influenciador na manifestação da desigualdade socioespacial nesse município. Como metodologia, utiliza-se 1) a análise da distribuição de equipamentos urbanos e 2) apresenta-se uma análise dos indicadores sociais referentes a essa ocupação irregular, iniciada na década de 1960. Os dados estatísticos disponibilizados em escala de Setores Censitários possibilitam identificar apenas até certo nível a relação entre a localização dos corpos d’água e a distribuição das classes socioeconômicas. Por outro lado, devido à baixa densidade demográfica das áreas estudadas e ao fato de os setores abrangerem uma área muito extensa em número de quadras, nota-se limitação desse método para identificar de forma objetiva e específica a localização de populações de baixa e alta renda dentro de um mesmo setor. Assim, conclui-se que estudos relativos à ocupação irregular em margens de córregos em situação de densidade demográfica semelhante à de Ponta Grossa – PR –  Brasil devem apoiar-se em levantamentos mais específicos, como atividades de campo, a fim de especificar e aprofundar os apontamentos gerados pelas análises de laboratório que têm por base os dados censitários. Aponta-se, assim, a necessidade de repensar o uso amplamente difundido de análises censitárias como únicas fontes de dados estatísticos para o desenvolvimento de políticas públicas e decisões de gestão urbana em geral.
A utilização da narrativa transmídia na construção de um recurso educacional aberto: estudo de caso da franquia Star Wars
Authors: Porto Cristiane de Magalhães , Nascimento Cleon Menezes do , Benia Renata Tavares
Published: June 2022

Com o advento da web 2.0, os usuários da rede deixaram de ser meros receptores de informações e passaram a assumir um papel proeminente de produtor de informações. Ao que alude tal panorama, surgem as narrativas transmídias. O presente artigo visa apresentar uma discussão a respeito do universo da transmídia em união aos Recursos Educacionais Abertos, contemplando a presença destes no âmbito educacional. Assim, exploram-se as descrições e levanta-se uma discussão acerca de tais universos realçados, tendo em vista o viés educativo. Ao observar estes universos, foi utilizada a franquia Star Wars para o desenvolvimento de uma intervenção metodológica para disciplina de Física com alunos de Engenharia, em razão de sua história poder auxiliar na transmissão de diversos conteúdos.
Expediente e Sumário
Authors: Mezzomo Frank Antônio
Published: June 2022

Expediente e Sumário
Expediente e sumário
Authors: Mezzomo Frank Antônio
Published: June 2022

Expediente e Sumário
Cyberbullying in a Multicultural Context—Forms, Strain, and Coping Related to Ethnicity-Based Cybervictimization
Authors: Schultze-Krumbholz Anja , Pfetsch Jan S. , Lietz Katrin
Published: June 2022

Cyberbullying is repeated aggressionviadigital media. There is extensive research analyzing forms of cyberbullying (e.g., relational or picture-based cyberbullying) and coping reactions (e.g., passive coping, seeking social support, retaliation). However, the mechanisms of cyberbullying in a multicultural society are not well-understood yet. Studies from the US show lower rates of cybervictimization for ethnic minorities, but comparable outcomes, studies from outside the US show different results. The present study focuses on the prevalence of ethnic/racist motives for cybervictimization as compared to non-ethnic/racist motives among adolescent students in a sample from Germany. Moreover, this study examines whether students with a migration background experience more strain and employ the same coping strategies as students without a migration background. An ethnically diverse sample ofN= 348 adolescents, agedM= 14.1 (SD= 1.2) years, 50% males, completed a questionnaire about cyberbullying, perceived strain, motives for cybervictimization and coping behavior. Twenty-one percentage of the sample had no, 14% had a first-generation, and 66% had a second-generation migration background. Adolescents with a migration background generally reported higher levels of all victimization motives. No difference in perceived strain was found between the migration status groups. Ethnicity-based motives only significantly predicted ethnic/racist victimization, while dispute-related motives predicted all types of cybervictimization. First-generation migration background, ethnicity-based cybervictimization and perceived strain all played an important role in the different coping strategies. In sum, ethnic/racist cybervictimization seems prevalent especially among first generation adolescents, who are affected in a comparable manner as non-immigrants. Adolescents with a first-generation migration background seem to be especially vulnerable. Prevention and intervention efforts should focus on functional coping strategies especially for this group on the one hand. On the other hand, evidence-based intervention programs should be implemented to reduce bias and ethnicity-/race-based perpetration and victimization to foster successful acculturation and integration.
Health and Well-Being in Surviving Congenital Heart Disease Patients: An Umbrella Review With Synthesis of Best Evidence
Authors: Cocomello Lucia , Taylor Kurt , Caputo Massimo , Cornish Rosie P. , Lawlor Deborah A.
Published: June 2022

Background

Advances in the management of congenital heart disease (CHD) patients have enabled improvement in long-term survival even for those with serious defects. Research priorities (for patients, families and clinicians) have shifted from a focus on how to improve survival to exploring long-term outcomes in patients with CHD. A comprehensive appraisal of available evidence could inform best practice to maximize health and well-being, and identify research gaps to direct further research toward patient and clinical need. We aimed to critically appraise all available published systematic reviews of health and well-being outcomes in adult patients with CHD.

Methods

We conducted an umbrella review, including any systematic reviews that assessed the association of having vs. not having CHD with any long-term health (physical or mental), social (e.g., education, occupation) or well-being [e.g., quality of life (QoL)] outcome in adulthood (≥18-years).

Results

Out of 1330 articles screened, we identified five systematic reviews of associations of CHD with adult outcomes. All but one (which studied QoL) explored health outcomes: one cardiovascular, two mental, and one mortality after transplant. CHD patients had a higher risk of stroke, coronary heart disease and heart failure, with the pooled relative risk (RR) for any outcome of 3.12 (95% CI: 3.01 to 3.24), with substantial heterogeneity (I2 = 99%) explained by the outcome being studied (stronger association for heart failure) and geography (stronger in Europe compared with other regions). CHD patients had a higher risk of anxiety (OR = 2.58 (1.45 to 4.59)], and higher mean scores for depression/anxiety symptoms (difference in means = −0.11 SD (–0.28 to 0.06), I2 = 94%)]. Compared with patients having a cardiac transplant for other (non-CHD) diseases, CHD patients had higher short-term mortality (RR at 30-days post-transplant = 2.18 [1.62 to 2.93)], with moderate heterogeneity (I2 = 41%) explained by previous surgery (higher mortality with prior Fontan/Glenn operation). All domains of QoL were lower in patients with Fontan’s circulation than non-CHD adults.

Conclusion

Adults with CHD have poorer cardiovascular, mental health and QoL outcomes, and higher short-term mortality after transplant. The paucity of systematic reviews, in particular for outcomes such as education, occupation and lifestyles, highlights the need for this to be made a priority by funders and researchers.

Systematic Review Registration

[www.crd.york.ac.uk/prospero], identifier [CRD42020175034].
Normalization of Four Different Types of Pulmonary Hypertension After Atrial Septal Defect Closure
Authors: Rubáčková Popelová Jana , Tomek Jakub , Tomková Markéta , Živná Renata
Published: June 2022

Pulmonary hypertension (PH) is an established risk factor in patients with atrial septal defect (ASD), and its persistence after ASD closure is associated with increased mortality. Therefore, predictors for PH normalization after defect closure are needed. Multiple hemodynamic types of PH exist, but little is known about their prevalence and prognostic value for PH normalization after ASD closure. We carried out a retrospective study on 97 patients (76% female, median age at ASD closure 58 years) with four types of PH determined predominantly by right heart catheterization: hyperkinetic, pulmonary arterial hypertension, isolated post-capillary, and combined pre- and post-capillary. We investigated the frequency of the PH types and their prognostic significance for PH normalization after ASD closure. Frequency of PH types before ASD closure in our study was: hyperkinetic 55%, pulmonary arterial hypertension 10%, isolated post-capillary PH 24%, and combined PH 11%. Hyperkinetic PH type was positively associated with PH normalization after ASD closure (78% patients normalized), remaining a significant independent predictor when adjusted for age at closure, sex, heart failure, and NYHA. Hyperkinetic PH patients also had significantly better survival prognosis versus patients with other PH types (p = 0.04). Combined PH was negatively associated with PH normalization, with no patients normalizing. Pulmonary arterial hypertension and isolated post-capillary PH had intermediate rates of normalization (60 and 52%, respectively). In summary, all four hemodynamic types of PH are found in adult patients with ASD, and they can be used to stratify patients by their likelihood of PH normalization and survival after ASD closure.
Cardiovascular Effects of Whole-Body Cryotherapy in Non-professional Athletes
Authors: Coppi Francesca , Pinti Marcello , Selleri Valentina , Zanini Giada , D'Alisera Roberta , Latessa Pasqualino Maietta , Tripi Ferdinando , Savino Gustavo , Cossarizza Andrea , Nasi Milena , Mattioli Anna Vittoria
Published: June 2022

Objectives:

The study aimed to investigate changes in heart rate, blood pressure, respiratory rate, oxygen saturation, and body temperature in non-professional trained runners during whole body cryotherapy (WBC).

Methods

Ten middle-distance runners received 3 once-a-day sessions of WBC. Subjects underwent BP measurements and ECG recorded before and immediately after the daily WBC session. During WBC we recorded a single lead trace (D1) for heart rhythm control. In addition, the 5 vital signs Blood pressure, heart rate, respiratory rate, oxygen saturation, and body temperature were monitored before, during, and after all WBC session.

Results

We did not report significant changes in ECG main intervals (PR, QT, and QTc). Mean heart rate changed from 50.98 ± 4.43 bpm (before) to 56.83 ± 4.26 bpm after WBC session (p < 0.05). The mean systolic blood pressure did not change significantly during and after WBC [b baseline: 118 ± 5 mmHg, changed to 120 ± 3 mmHg during WBC, and to 121 ± 2 mmHg after session (p < 0.05 vs. baseline)]. Mean respiratory rate did not change during WBC as well as oxygen saturations (98 vs. 99%). Body temperature was slightly increased after WBC, however it remains within physiological values

Conclusion

In non-professional athletes WBC did not affect cardiovascular response and can be safely used. However, further studies are required to confirm these promising results of safety in elderly non-athlete subjects.
Association Between Prognostic Nutritional Index and Prognosis in Patients With Heart Failure: A Meta-Analysis
Authors: Chen Mei-Yu , Wen Jiang-Xiong , Lu Mei-Ting , Jian Xiang-Yu , Wan Xiao-Liang , Xu Zhi-Wen , Liang Jian-Qiu , Wu Jian-Di
Published: June 2022

Background

The prognostic nutritional index (PNI) has been proposed as a marker of malnutrition and associated with the prognosis of cardiovascular disease. However, whether PNI can serve as a potential biomarker for the prognosis of heart failure (HF) upon those established risk factors were still controversial. This meta-analysis aimed to generate comprehensive evidence on the prognostic value of PNI in patients with HF.

Methods

Multiple databases (PubMed, Embase, the Cochrane Library, and Google Scholar) were searched for related studies up to January 31, 2022. Observational studies accessed associations between PNI levels and the prognosis in patients with HF were included for meta-analysis. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated.

Results

Fourteen studies, comprising 19,605 patients with HF were included for meta-analysis. The median follow-up duration was 18.5 months. Compared with those with higher PNI (normal nutritional status), patients with HF with lower PNI (malnourished) were associated with a higher risk of all-cause mortality (HR 1.53, 95% CI 1.27–1.85) and composite major adverse cardiac outcomes (MACEs; HR 2.26, 95% CI 1.54–3.31) in the multivariable-adjusted model. Furthermore, when PNI was defined as per 1 increment as a continuous metric, higher PNI was associated with a decrease in all-cause mortality (per 1 increment of PNI: HR 0.94, 95% CI 0.88–0.96) and MACEs (per 1 increment of PNI: HR 0.97, 95% CI 0.95–0.98).

Conclusions

The PNI can serve as an easily calculated bedside “malnutrition-inflammation” biomarker in HF. Lower PNI was associated with a worse prognosis in patients with HF.
Case Report: An Unusual Case of Pheochromocytoma
Authors: Liao Ying , Shi Shanshan , Liao Lihua , Zhao Yukun , Lin Rongwen , Chen Kaihong
Published: June 2022

Pheochromocytoma is a benign catecholamine secreting tumor, which is rare and originates from the adrenal gland. It has been known for a wide range of clinical manifestations and can mimic other difficult-to-diagnose diseases. Here, we report a female patient with acquired long QT syndrome, which is a rare complication of pheochromocytoma. Although relatively rare, the presence of pheochromocytoma should be considered in the case of malignant arrhythmias and electrocardiographic changes in patients.
Analysis of the Influence of Thyroid Nodule Characteristics on the Results of Shear Wave Elastography
Authors: Xue Ji-ping , Kang Xiao-yan , Miao Jun-wang , Zhang Yan-xia , Li Hui-zhan , Yao Fu-cheng , Kang Chun-song
Published: June 2022

Objective

To analyze the ultrasonic characteristics of false-negative and false-positive results of shear wave elastography (SWE) in the diagnosis of thyroid nodules to clarify the influence of nodular characteristics on SWE and to guide the clinical application of SWE.

Methods

A total of 435 thyroid nodules from 343 patients with the diagnosis confirmed by surgical pathology were analyzed. Preoperative ultrasonography and SWE were conducted. The conventional ultrasound characteristics of thyroid nodules and the maximum Young’s modulus were recorded. The false negativity and false positivity of SWE for the diagnosis of thyroid nodules were calculated. The ultrasonic characteristics of thyroid nodules with SWE false results were analyzed, and logistic regression analysis was adopted to determine the ultrasonic characteristics associated with SWE false results of thyroid nodules.

Results

Among 323 malignant nodules, the SWE false negativity was 27.2% (88/323). The false positivity of SWE in 112 benign nodules was 19.6% (22/112). Regression analysis showed that an increase in the nodule volume increased the risk of SWE false-positive results (odds ratio [OR] 3.286; 95% confidence interval [CI]: 1.572–6.871; P = 0.002) and decreased the risk of false-negative results (OR 0.238; 95% CI: 0.115–0.493; P < 0.001). Nodules with coarse calcification had an increased risk of SWE false-positive results compared with those without calcification (OR 5.303; 95% CI: 1.098–25.619; P = 0.038). However, nodules with scattered hyperechoic foci had a reduced risk of SWE false-negative results (OR 0.515; 95% CI: 0.280–0.951; P = 0.034).

Conclusion

Nodular size and calcification were correlated with SWE false results, and the clinical application of SWE should be combined with conventional ultrasound features. Fine needle aspiration or a puncture biopsy should be conducted if necessary.
Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria
Authors: Ladjouze Asmahane , Donaldson Malcolm , Plotton Ingrid , Djenane Nacima , Mohammedi Kahina , Tardy-Guidollet Véronique , Mallet Delphine , Boulesnane Kamélia , Bouzerar Zair , Morel Yves , Roucher-Boulez Florence
Published: June 2022

Background

3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world literature and few data on outcomes.

Patients and Methods

We report a mixed longitudinal and cross-sectional study from a single Algerian center between 2007 and 2021. Virilization and under-masculinization were assessed using Prader staging and the external masculinization score (EMS), pubertal development staged according to the system of Tanner. Adrenal steroids were measured using mass spectrophotometry (LC-MS/MS). A genetic analysis of HSD3B2 was performed using Sanger sequencing.

Results

A 3βHSD2 defect was confirmed in 6 males and 8 females from 10 families (8 consanguineous), with p.Pro222Gln mutation in all but two siblings with a novel deletion: c.453_464del or p.(Thr152_Pro155del). Probable 3βHSD2 deficiency was diagnosed retrospectively in a further 6 siblings who died, and in two patients from two other centers. In the genetically confirmed patients, the median (range) age at presentation was 20 (0–390) days, with salt-wasting (n = 14) and genital anomaly (n = 10). The Prader stage for female patients was 2 (1–2) with no posterior fusion of the labia. The EMS for males was 6 (3–9). Median (range) values at diagnosis for 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxypregnenolone (17OHPreg) were elevated: 73.7 (0.37–164.3) nmol/L; 501.2(9.4–5441.3) nmol/L, and 139.7 (10.9–1500) nmol/l (NB >90 nmol/L diagnostic of 3βHSD2 defect). Premature pubarche was observed in four patients (3F:1M). Six patients (5F:1M) entered puberty spontaneously, aged 11 (5–13) years in 5 girls and 11.5 years in one boy. Testicular adrenal rest tumors were found in three boys. Four girls reached menarche at 14.3 (11–14.5) years, with three developing adrenal masses (surgically excised in two) and polycystic ovary syndrome (PCOS), with radiological evidence of ovarian adrenal rest tumor in one. The median IQ was 90 (43–105), >100 in only two patients and <70 in three.

Conclusions

The prevalence of 3βHSD2 deficiency in Algeria appears high, with p.Pro222Gln being the most frequent mutation. Mortality is also high, with significant morbidity from adrenal tumors and PCOS in adolescence and an increased risk of learning disability. The finding of adrenal tumors in older patients with 3βHSD2 indicates under-replacement, requiring effective hydrocortisone and fludrocortisone treatment rather than surgical removal.
Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft
Authors: Chen Pengfei , Yao Fuwen , Lu Ying , Peng Yuanzheng , Zhu Shufang , Deng Jing , Wu Zijing , Chen Jiao , Deng Kai , Li Qi , Pu Zuhui , Mou Lisha
Published: June 2022

Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8+ T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.
Efficacy of Whole-Blood Exchange Transfusion in Refractory Severe Autoimmune Haemolytic Anaemia Secondary to Systemic Lupus Erythematosus: A Real-World Observational Retrospective Study
Authors: Jiang Ying , Zhao Hong Jun , Luo Hui , Li Bi Juan , Zhang Zhi Min , Zhao Li Dan , Zuo Xiao Xia
Published: June 2022

Background

Severe autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs.

Methods

In this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX).

Results

Among the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3’s cost of hospitalisation is more than groups 1 and 2. Hbmin <40 g/L may be a key indicative factor for initiating WBE remedy therapy as IVIG/RTX may not be effective enough in 48–72 h in those patients with refractory severe SLE-AIHA. No severe adverse effects were observed in the WBE group.

Conclusions

WBE could be a safe and beneficial alternative therapy for refractory severe SLE-AIHA.
Serum Proteomic Analysis Identifies SAA1, FGA, SAP, and CETP as New Biomarkers for Eosinophilic Granulomatosis With Polyangiitis
Authors: Xiao Jing , Lu Shaohua , Wang Xufei , Liang Mengdi , Dong Cong , Zhang Xiaoxian , Qiu Minzhi , Ou Changxing , Zeng Xiaoyin , Lan Yanting , Hu Longbo , Tan Long , Peng Tao , Zhang Qingling , Long Fei
Published: June 2022

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by asthma-like attacks in its early stage, which is easily misdiagnosed as severe asthma. Therefore, new biomarkers for the early diagnosis of EGPA are needed, especially for differentiating the diagnosis of asthma.

Objectives

To identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma.

Method

Data-independent acquisition (DIA) analysis was performed to identify 45 healthy controls (HC), severe asthma (S-A), and EGPA patients in a cohort to screen biomarkers for early diagnosis of EGPA and to differentiate asthma diagnosis. Subsequently, parallel reaction monitoring (PRM) analysis was applied to a validation cohort of 71 HC, S-A, and EGPA patients.

Result

Four candidate biomarkers were identified from DIA and PRM analysis—i.e., serum amyloid A1 (SAA1), fibrinogen-α (FGA), and serum amyloid P component (SAP)—and were upregulated in the EGPA group, while cholesteryl ester transfer protein (CETP) was downregulated in the EGPA group compared with the S-A group. Receiver operating characteristics analysis shows that, as biomarkers for early diagnosis of EGPA, the combination of SAA1, FGA, and SAP has an area under the curve (AUC) of 0.947, a sensitivity of 82.35%, and a specificity of 100%. The combination of SAA1, FGA, SAP, and CETP as biomarkers for differential diagnosis of asthma had an AUC of 0.921, a sensitivity of 78.13%, and a specificity of 100%, which were all larger than single markers. Moreover, SAA1, FGA, and SAP were positively and CETP was negatively correlated with eosinophil count.

Conclusion

DIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma.
Immunosuppressant Treatment in Rheumatic Musculoskeletal Diseases Does Not Inhibit Elicitation of Humoral Response to SARS-CoV-2 Infection and Preserves Effector Immune Cell Populations
Authors: Favalli Andrea , Favalli Ennio Giulio , Gobbini Andrea , Zagato Elena , Bombaci Mauro , Maioli Gabriella , Pesce Elisa , Donnici Lorena , Gruarin Paola , Biggioggero Martina , Curti Serena , Manganaro Lara , Marchisio Edoardo , Bevilacqua Valeria , Martinovic Martina , Fabbris Tanya , Sarnicola Maria Lucia , Crosti Mariacristina , Marongiu Laura , Granucci Francesca , Notarbartolo Samuele , Bandera Alessandra , Gori Andrea , De Francesco Raffaele , Abrignani Sergio , Caporali Roberto , Grifantini Renata
Published: June 2022

COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated analysis of the immune response following SARS-CoV-2 infection in RMD patients treated with different classes of DMARDs we carried out an immunological analysis of the antibody responses toward SARS-CoV-2 nucleocapsid and RBD proteins and an extensive immunophenotypic analysis of the major immune cell populations. We showed that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus, with neutralizing activity. In addition, they displayed a sizable percentage of effector T and B lymphocytes. Among b-DMARDs, we found that anti-TNFα treatments are more favorable drugs to elicit humoral and cellular immune responses as compared to CTLA4-Ig and anti-IL6R inhibitors. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF-α inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections.
Neutrophil Extracellular Traps, Sepsis and COVID-19 – A Tripod Stand
Authors: Ventura-Santana Esmeiry , Ninan Joshua R. , Snyder Caitlin M. , Okeke Emeka B.
Published: June 2022

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Majority of COVID-19 patients have mild disease but about 20% of COVID-19 patients progress to severe disease. These patients end up in the intensive care unit (ICU) with clinical manifestations of acute respiratory distress syndrome (ARDS) and sepsis. The formation of neutrophil extracellular traps (NETs) has also been associated with severe COVID-19. Understanding of the immunopathology of COVID-19 is critical for the development of effective therapeutics. In this article, we discuss evidence indicating that severe COVID-19 has clinical presentations consistent with the definitions of viral sepsis. We highlight the role of neutrophils and NETs formation in the pathogenesis of severe COVID-19. Finally, we highlight the potential of therapies inhibiting NETs formation for the treatment of COVID-19.
Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma
Authors: Zhang Jing , Zou Yuan , Chen Longmin , Xu Qianqian , Wang Yi , Xie Min , Liu Xiansheng , Zhao Jianping , Wang Cong-Yi
Published: June 2022

Asthma is a multifactorial disorder characterized by the airway chronic inflammation, hyper-responsiveness (AHR), remodeling, and reversible obstruction. Although asthma is known as a heterogeneous group of diseases with various clinical manifestations, recent studies suggest that more than half of the clinical cases are ‘‘T helper type 2 (Th2)-high’’ type, whose pathogenesis is driven by Th2 responses to an inhaled allergen from the environmental exposures. The intensity and duration of inflammatory responses to inhaled allergens largely depend on the balance between effector and regulatory cells, but many questions regarding the mechanisms by which the relative magnitudes of these opposing forces are remained unanswered. Regulatory T cells (Tregs), which comprise diverse subtypes with suppressive function, have long been attracted extensive attention owing to their capability to limit the development and progression of allergic diseases. In this review we seek to update the recent advances that support an essential role for Tregs in the induction of allergen tolerance and attenuation of asthma progression once allergic airway inflammation established. We also discuss the current concepts about Treg induction and Treg-expressed mediators relevant to controlling asthma, and the therapies designed based on these novel insights against asthma in clinical settings.
Who Is in Handicrafts: Tooth Morphology and Age Determination as Tools to Assess Vulnerable Dolphins Sotalia spp. Supplying the Trade of Artisanal Charms in Brazil
Authors: Ruenes Greicy F. , Oliveira Larissa R. de , Emin-Lima Renata , Costa Alexandra Fernandes , Attademo Fernanda Löffler Niemeyer , Luna Fábia de Oliveira , Siciliano Salvatore
Published: June 2022

In Brazil, dolphins’ body parts are commonly used as traditional amulets, named as love-charms, while dolphins’ teeth are commercialized in handcrafted necklaces and bracelets. Recent studies on forensic genetics confirmed the Guiana dolphin,Sotalia guianensis, as the principal target of the love-charms trading, with specimens incidentally captured in gillnets suggested as the primary source. As additional support for these investigations, we characterized tooth morphotypes and ages of dolphins used in the construction of traditional crafts, with the main objective of detecting the dolphin species and population groups most affected by this trade. Teeth collected from necklaces, bracelets, and earrings, sold in public markets from three major cities of Northern and Northeastern Brazil (Belém = 99, São Luís = 4, and Fortaleza =15), were analyzed using four morphological measurements: tooth total length (TL), root diameter (RD), crown length (CL), and cingulum diameter (CID). An unweighted pair group method using arithmetic means (UPGMA), with Euclidean distances as a measure of dissimilarity, multivariate analysis of variance (MANOVA), and principal component analysis (PCA) were used to detect tooth morphotypes in the samples. Ages were obtained by counting the growth layer groups (GLGs) deposited in dentine. Two different groups of teeth were detected presumably belonging to the speciesSotalia guianensisandS. fluviatilis. Handicrafts showed a diverse age composition, ranging from 2 to 30 years, with a multimodal distribution (Mean =11 ± 7 SD, Median = 10, Mode = 4, 8, 19), similar to dolphin populations affected by fishery interaction. Results suggested that juveniles individuals and adults younger than 20 years, from bothSotaliaspecies, probably incidentally captured, are the principal source of handicrafts, and raise concern about the greater vulnerability of young age categories presented in this trade.
Seasonal and Long-Term Variability of the Mixed Layer Depth and its Influence on Ocean Productivity in the Spanish Gulf of Cádiz and Mediterranean Sea
Authors: Vargas-Yáñez Manuel , Moya Francina , Balbín Rosa , Santiago Rocío , Ballesteros Enrique , Sánchez-Leal Ricardo F. , Romero Patricia , García-Martínez Ma Carmen
Published: June 2022

The warming of the surface ocean is expected to increase the stratification of the upper water column. This would decrease the efficiency of the wind-induced mixing, reducing the nutrient supply to the euphotic layer and the productivity of the oceans. Climatic projections show that the Mediterranean Sea will experience a strong warming and salting along the twenty first century. Nevertheless, very few works have found and quantified changes in the water column stratification of the Western Mediterranean. In this work, we obtain time series of Mixed Layer Depth (MLD) along the Spanish Mediterranean waters and the Gulf of Cádiz, using periodic CTD profiles collected under the umbrella of the Ocean Observing system of the Instituto Español de Oceanografía (IEO-CSIC). The length of the time series analyzed is variable, depending on the geographical area, but in some cases these time series extend from the beginning of the 1990s decade. Our results show that at present, no statistically significant changes can be detected. These results are confirmed by the analysis of MLD time series obtained from Argo profilers. Some of the meteorological factors that could affect the water column stratification (wind intensity and precipitation rates) did not experience significant changes for the 1990-2021 period, neither were observed long-term changes in the chlorophyll concentration. The hypothesis proposed to explain this lack of trends, is that the salinity increase of the surface waters has compensated for the warming, and consequently, the density of the upper layer of the Western Mediterranean (WMED) has remained constant. As the wind intensity has not experienced significant trends, the stratification of the Spanish Mediterranean waters and those of the Gulf of Cádiz would have not been affected. Nevertheless, we do not discard that our results are a consequence of the short length of the available time series and the large variance of the variables analyzed, evidencing the importance of the maintenance of the ocean monitoring programs.
Dietary Arginine Modulates Growth Performance, Hemato-Biochemical Indices, Intestinal Enzymes, Antioxidant Ability and Gene Expression of TOR and 4E-BP1 in Rainbow Trout, Oncorhynchus mykiss Fingerlings
Authors: Ahmed Imtiaz , Ahmad Ishtiyaq , Malla Bashir Ahmad , Shah Basit Amin , Wani Zubair Ahmad , Khan Younis Mohd
Published: June 2022

We evaluated the effect of arginine on growth, hemato-biochemical variables, intestinal enzymes, antioxidant ability, and expression of target of rapamycin (TOR) signaling pathway related genes in fingerling Oncorhynchus mykiss. A series of six uniform diets consisting of 450 g kg-1 of protein and 20.9 g-1 of energy with graduated levels (10.0, 12.5, 15.0, 17.5, 20.0, and 22.5 g kg-1) of arginine were formulated. Significant (p < 0.05) variations were observed in various analyzed parameters. Growth parameters showed a positive linear trend with increasing arginine levels up to 17.5 g kg-1. Fish offered 17.5 g kg-1 of dietary arginine exhibited highest body protein, lowest moisture, and intermediate fat contents, whereas, body ash content did not significantly (p > 0.05) change with respect to each dietary arginine offered diet, except for the lowest levels. Each group also produced significant (p < 0.05) changes in their hematological variables with maximum hemoglobin (Hb), hematocrit (Hct) content, and red blood cell (RBC) count noted at 17.5 g kg-1 arginine diet. Although the majority of blood plasma parameters were insignificantly (p > 0.05) different with respect to varied arginine fed diets, plasma aspartate transaminase (AST) showed significant (p < 0.05) variations across the treatments. Moreover, total protein, alkaline phosphatase (ALP) and albumin contents increased significantly (p < 0.05) with increasing arginine concentrations up to 17.5 g kg-1 and, thereafter, a declined trend in these parameters were noted. Intestinal enzymes and antioxidant properties showed significant (p < 0.05) variations, except plasma amylase, which showed insignificant variation. The maximum up-regulation of TOR and 4E-BP1 gene expression levels were found for fish fed 17.5 g kg-1 of dietary arginine compared to the lower (10.0 and 12.5 g kg-1) and higher (20.0 and 22.5 g kg-1) arginine levels, which indicates that fish utilize arginine more efficiently at this point. Quadratic regression analysis of live weight gain (LWG), feed conversion ratio (FCR), protein efficiency ratio (PER) and body protein deposition (BPD) indicated the optimal arginine requirement of rainbow trout to be 17.61 g kg-1 of dry diet, corresponding to 39.13 g kg-1 of dietary protein, which enhances growth, immunity, antioxidant ability, and also promote TOR signaling pathway in rainbow trout.
A Height-Based Dosing Algorithm of Bupivacaine in Spinal Anesthesia for Decreasing Maternal Hypotension in Cesarean Section Without Prophylactic Fluid Preloading and Vasopressors: A Randomized-Controlled Non-Inferiority Trial
Authors: Huang Qiang , Wen Gengzhi , Hai Chao , Zheng Zihao , Li Yali , Huang Zengping , Huang Bowan
Published: June 2022

Background

There is a high incidence of maternal hypotension in spinal anesthesia for cesarean section. The aim of the study is to investigate whether there is a height-based dosing algorithm of bupivacaine that provides adequate anesthesia with less maternal hypotension.

Methods

There were 2 groups of 280 parturients who did not receive prophylactic fluid preloading: Test and Conventional group. In Test group, a height based dosing algorithm was used to confirm the dose of bupivacaine in parturients without prophylactic vasopressors. In the Conventional group, a constant dose of bupivacaine was used. The complications and quality of anesthesia were evaluated.

Results

In the Conventional group, the shorter participants had higher incidence of hypotension, faster sensory block time, and more participants with complete motor block (p = 0.030, 2.957 × 10−14, and 0.012). In the Test group, the incidence of hypotension, sensory block time, and number of participants with complete motor block did not change with height (p = 0.199, 0.617, and 0.209). The height-based dosing algorithm of bupivacaine decreased the incidence of hypotension (p = 0.004), induced lower sensory block level and less degree of motor block (p = 3.513 × 10−7 and 5.711 × 10−11). The quality of analgesia, quality of muscle relaxation, and degree of intraoperative comfort were similar in both groups (p = 0.065, 0.498, and 0.483).

Conclusions

The height influences the dose of bupivacaine in spinal anesthesia; without prophylactic fluid pre-loading and vasopressors, the height-based dosing algorithm of bupivacaine is suitable, and meets the cesarean section' requirement with less maternal hypotension.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier: NCT03497364.
Bevacizumab Eye Drops Vs. Intra-meibomian Gland Injection of Bevacizumab for Meibomian Gland Dysfunction-Associated Posterior Blepharitis
Authors: Tantipat Chitchanok , Kasetsuwan Ngamjit , Chotikkakamthorn Patraramon , Pongpirul Krit
Published: June 2022

Aims

This study aimed to evaluate the efficacy and safety of bevacizumab eye drops compared with those of an intra-meibomian gland (MG) injection of bevacizumab when performed in conjunction with standard lid hygiene in patients with meibomian gland dysfunction (MGD)-associated posterior blepharitis.

Methods

This prospective, open-label, observer-blinded randomized controlled trial included 60 eyes of 30 patients with MGD-associated posterior blepharitis who exhibited lid margin telangiectasia, treated at the Chula Refractive Surgery Center of King Chulalongkorn Memorial Hospital. Patients were randomized to receive lid hygiene plus 0.05% bevacizumab eye drops or a single intra-MG injection of 2.5% bevacizumab. All patients were instructed to perform routine lid hygiene care as demonstrated in an instructional video. Primary outcomes included telangiectasia grading and the lid margin neovascularized area (LMNA). Secondary outcomes included the Ocular Surface Disease Index (OSDI) score, corneal staining, meibum quality, meiboscore, conjunctival redness, fluorescein break-up time (FBUT), lipid layer thickness, treatment compliance, and adverse events. All parameters were evaluated before and 3 months after treatment.

Results

After treatment, there were no significant differences in telangiectasia grade and LMNA between groups (mean difference, −0.14, 95% CI −0.42 to 0.15, p = 0.338, −0.1, 95% CI −1.1 to 0.8, p = 0.761, respectively); however, the injection group exhibited significant improvements in both telangiectasia grade and LMNA, while, in the eye drop group, only telangiectasia grade showed a significant improvement relative to baseline. The injection group also exhibited significant improvements in corneal staining (mean difference, −0.78, 95% CI −1.29 to −0.27, p = 0.003), meiboscores (mean difference, −0.37, 95% CI −0.52 to −0.21, p <0.001), and FBUT (mean difference, 1.25, 95% CI 0.21–2.29, p = 0.019) compared to the eye drop group. OSDI scores, corneal staining, meibum quality, meiboscores, and conjunctival redness significantly improved relative to baseline in both groups. No local and systemic adverse event was observed at month 3 in both groups.

Conclusion

When performed with regular lid hygiene, intra-MG injection and topical application of bevacizumab are safe and effective for improving lid margin telangiectasia and the signs and symptoms of MGD-associated posterior blepharitis. This therapy may represent an alternative or adjunctive treatment for patients with MGD-associated posterior blepharitis.
Network Pharmacology-Based Investigation of the Molecular Mechanisms of the Chinese Herbal Formula Shenyi in the Treatment of Diabetic Nephropathy
Authors: Chen Keng , Deng Yiyao , Shang Shunlai , Li Ping , Liu Linchang , Chen Xiangmei
Published: June 2022

Background

The Chinese herbal formula Shenyi (SY) is a prescription that was developed by the Department of Nephrology, Chinese People's Liberation Army General Hospital. This preparation is mainly used to treat chronic kidney disease (CKD) caused by Diabetic nephropathy (DN) and is effective. However, the active ingredients of SY, DN treatment-related molecular targets and the effector mechanisms are still unclear.

Methods

The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the Traditional Chinese Medicine and Chemical Component Database of Shanghai Institute of Organic Chemistry were used to screen the active ingredients in SY, the TCMSP database and Swiss Target Prediction database were used to collect the targets of the active ingredients of SY, and the Gene Cards and Online Mendelian Inheritance in Man (OMIM) databases were used to screen for DN pathogenesis targets. The intersections of the component targets and disease targets were mapped to obtain the therapeutic targets. The METASCAPE database was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the therapeutic targets. Cytoscape 3.7.2 was used to analyze topological parameters and construct a network of SY for the treatment of DN.

Results

Sixty-two active ingredients and 497 active ingredient effector targets in SY, 3260 DN-related targets, and 271 SY treatments for DN targets were identified. Among these targets, 17 were core targets, including AKT1, tumor necrosis factor (TNF), interleukin-6 (IL6), and TP53. The GO and KEGG enrichment analyses show that SY's therapeutic effects for DN occur mainly through pathways such as advanced glycation end product (AGE)-RAGE, PI3K-Akt, and IL-17.

Conclusion

Multiple active ingredients in SY exhibit treatment effects on DN by affecting metabolism, inhibiting inflammation, and affecting cell structure growth.