bluuebunny/crossref_metadata_2025 huggingface dataset:
The mediatory role of Majie cataplasm on inflammation of allergic asthma through transcription factors related to Th1 and Th2
Authors: Ji Wenting , Zhang Qianyi , Shi Hanfen , Dong Ruijuan , Ge Dongyu , Du Xin , Ren Beida , Wang Xueqian , Wang Qingguo
Published: May 2020

Background

Asthma, a common respiratory disease, is harmful biological effect to our health. As a traditional Chinese medicine for asthma, Majie cataplasm could alleviate the symptoms of asthma and its compositions have immunomodulatory effects. Previous experiments showed that Majie cataplasm was an effective approach to mitigate asthma airway remodeling and had the potential to regulate Th2 cytokines of IL-5 and IL-13. Therefore, our further research focuses on the explanation about the regulatory effect of Majie cataplasm on reshaping Th1/Th2 through their related transcription factors.

Methods

In this experiment, the launch of asthma model was made by inducing with Ovalbumin (OVA) in C57 mice (n = 40), including 4 groups: the untreated control group (n = 10), the asthma model group (n = 10), the dexamethasone group (n = 10) and the Majie cataplasm group (n = 10). After the intervention, all groups of animals got detected for serum IgE levels, and HE staining of lung tissues was to observe and examine pathological changes. Meanwhile, we analyzed the secretion of IL-4+ T cells and IFN-γ+ T cells in spleen by flow cytometry. The expressions of transcription factor STAT6 mRNA, GATA-3 mRNA and T-bet mRNA in lung tissues was tested by PCR, and western blot had been used to detect levels of JAK2 and STAT3.

Results

We found that Majie cataplasm eased the content of serum IgE and lung inflammation. It could lower the increased number of IL-4+ T cells and IFN-γ+ T cells (P < 0.0001, P < 0.01) in asthmatic mice and curb the expression of STAT6 mRNA and GATA-3 (P < 0.0001, P < 0.01) mRNA as well as the protein levels of JAK2 (P < 0.001) and the ratio of pSTAT3/STAT3 (P < 0.05). Besides, Majie cataplasm made its mark on T-bet mRNA by improving it (P < 0.0001).

Conclusion

These data suggest that Majie cataplasm exert an anti-inflammatory effect of Th2 by rebalancing Th1/Th2 through corresponding transcription factor STAT6, GATA-3, STAT3, and T-bet, which providing a strong cornerstone for asthma control.
Frizzled related protein deficiency impairs muscle strength, gait and calpain 3 levels
Authors: Casas-Fraile Leire , Cornelis Frederique M. , Costamagna Domiziana , Rico Anabel , Duelen Robin , Sampaolesi Maurilio M. , López de Munain Adolfo , Lories Rik J. , Sáenz Amets
Published: May 2020

Background

Limb-girdle muscular dystrophy recessive 1 calpain3-related (LGMDR1), previously known as LGMD2A, is a disease caused by mutations in the CAPN3 gene. It is characterized by progressive weakness and muscle degeneration. Frizzled related protein (FRZB), upregulated in LGMDR1, was identified as a key regulator of the crosstalk between Wnt and integrin signalling pathways. FRZB gene silencing showed a recovery in the expression of some of the costamere protein levels in myotubes.

Results

Here, we performed a comprehensive characterization of Frzb−/− mice muscles to study the absence of Frzb in skeletal muscle and eventual links with the molecular characteristics of LGMDR1 patient muscles. Frzb−/− mice showed reduced muscle size and strength. Gait analysis showed that Frzb−/− mice moved more slowly but no impaired regeneration capacity was observed after muscle injury. Additionally, Frzb−/− mice muscle showed an increased number of mesoangioblasts. Lack of Frzb gene in Frzb−/− mice and its increased expression in LGMDR1 patients, showed contrary regulation of Rora, Slc16a1, Tfrc and Capn3 genes. The reciprocal regulation of Frzb and Capn3 genes further supports this axis as a potential target for LGMDR1 patients.

Conclusions

Our data confirm a role for Frzb in the regulation of Rora, Slc16a1, Tfrc, and Capn3 genes in muscle cells. In vivo, reduced muscle strength and gait in the Frzb−/− mice are intriguing features. The reciprocal relationship between FRZB and CAPN3 further supports a key role for this axis in patients with LGMDR1.
Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients
Authors:   the OrphaLung network, Daccord C. , Cottin V. , Prévot G. , Uzunhan Y. , Mornex J. F. , Bonniaud P. , Borie R. , Briault A. , Collonge-Rame M. A. , Crestani B. , Devouassoux G. , Freynet O. , Gondouin A. , Hauss P. A. , Khouatra C. , Leroy S. , Marchand-Adam S. , Marquette C. , Montani D. , Naccache J. M. , Nadeau G. , Poulalhon N. , Reynaud-Gaubert M. , Salaun M. , Wallaert B. , Cordier J. F. , Faouzi M. , Lazor R.
Published: May 2020

Background

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD.

Results

Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years.

Conclusions

Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.
Study on depressive symptoms in patients with Mayer-Rokitansky-Küster-Hauser syndrome: an analysis of 141 cases
Authors: Chen Na , Song Shuang , Duan Yanping , Kang Jia , Deng Shan , Pan Hongxin , Zhu Lan
Published: May 2020

Background

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital disease characterized by uterovaginal agenesis. The diagnosis of MRKH syndrome generally leads to considerable emotional burdens on patients. However, studies focusing on the psychological influence on patients are limited and of unsatisfactory quality. The aim of this study was to investigate the prevalence of depressive symptoms in Chinese patients with MRKH syndrome and to identify the factors associated with depressive symptoms. We recruited 141 patients with MRKH syndrome and 178 age-matched healthy women as control group in this cross-sectional study. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Other parameters such as sociodemographic characteristics, treatment histories, personality traits, and attitudes toward femininity and offspring, were also gathered in the self-administered questionnaire.

Results

The PHQ-9 score was significantly higher in MRKH patient group than the age-matched control group (7.0 (4.5–11.0) vs. 6.0 (3.0–9.0)), median and IQRs) (P = 0.015). A total of 75.2% of MRKH patients suffered from depressive symptoms, and 34.0% reached a moderate to severe level, while the proportion in the control group was 61.2 and 24.2% respectively. Compared with other age groups, patients in their 20s scored higher on the PHQ-9. Patients with higher neuroticism levels in personality traits (OR 1.19 95% CI 1.11–1.28), negative self-evaluation of femininity (OR 3.964, 95% CI 1.371–11.464) and sexual dysfunction (OR 4.81 95% CI 1.24–18.72) (compared with those having no sexual activity) were more likely to exhibit depressive symptoms.

Conclusions

Three-quarters of MRKH patients show depressive symptoms, and one-third of these individuals are even at risk for depressive disorders. Therefore, depressive symptom screening and proper psychotherapy in MRKH patients are of great importance.
Interleukin-6 deficiency exacerbates Huntington’s disease model phenotypes
Authors: Wertz Mary H. , Pineda S. Sebastian , Lee Hyeseung , Kulicke Ruth , Kellis Manolis , Heiman Myriam
Published: May 2020

Huntington’s disease (HD) is an incurable neurodegenerative disorder caused by CAG trinucleotide expansions in the huntingtin gene. Markers of both systemic and CNS immune activation and inflammation have been widely noted in HD and mouse models of HD. In particular, elevation of the pro-inflammatory cytokine interleukin-6 (IL-6) is the earliest reported marker of immune activation in HD, and this elevation has been suggested to contribute to HD pathogenesis. To test the hypothesis that IL-6 deficiency would be protective against the effects of mutant huntingtin, we generated R6/2 HD model mice that lacked IL-6. Contrary to our prediction, IL-6 deficiency exacerbated HD-model associated behavioral phenotypes. Single nuclear RNA Sequencing (snRNA-seq) analysis of striatal cell types revealed that IL-6 deficiency led to the dysregulation of various genes associated with synaptic function, as well as the BDNF receptor Ntrk2. These data suggest that IL-6 deficiency exacerbates the effects of mutant huntingtin through dysregulation of genes of known relevance to HD pathobiology in striatal neurons, and further suggest that modulation of IL-6 to a level that promotes proper regulation of genes associated with synaptic function may hold promise as an HD therapeutic target.
A systematic literature review of the ethics of conducting research in the humanitarian setting
Authors: Bruno William , Haar Rohini J.
Published: May 2020

Background

Research around humanitarian crises, aid delivery, and the impact of these crises on health and well-being has expanded dramatically. Ethical issues around these topics have recently received more attention. We conducted a systematic literature review to synthesize the lessons learned regarding the ethics of research in humanitarian crises.

Methods

We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to identify articles regarding the ethics of research in humanitarian contexts between January 1, 1997 and September 1, 2019. We analyzed the articles to extract key themes and develop an agenda for future research.

Results

We identified 52 articles that matched our inclusion criteria. We categorized the article data into five categories of analysis: 32 were expert statements, 18 were case studies, 11 contained original research, eight were literature reviews and three were book chapters. All included articles were published in English. Using a step-wise qualitative analysis, we identified 10 major themes that encompassed these concepts and points. These major themes were: ethics review process (21 articles, [40.38%]); community engagement (15 articles [28.85%]); the dual imperative, or necessity that research be both academically sound and policy driven, clinical trials in the humanitarian setting (13 articles for each, [25.0%)]; informed consent (10 articles [19.23%]); cultural considerations (6 articles, [11.54%]); risks to researchers (5 articles, [9.62%]); child participation (4 articles [7.69%]); and finally mental health, and data ownership (2 articles for each [3.85%]).

Conclusions

Interest in the ethics of studying humanitarian crises has been dramatically increasing in recent years. While key concepts within all research settings such as beneficence, justice and respect for persons are crucially relevant, there are considerations unique to the humanitarian context. The particular vulnerabilities of conflict-affected populations, the contextual challenges of working in humanitarian settings, and the need for ensuring strong community engagement at all levels make this area of research particularly challenging. Humanitarian crises are prevalent throughout the globe, and studying them with the utmost ethical forethought is critical to maintaining sound research principles and ethical standards.
Exploring perceived costs and benefits of first aid for youth with depression: a qualitative study of Japanese undergraduates
Authors: Kashihara Jun , Sakamoto Shinji
Published: May 2020

Background

Early interventions for depression among youth are greatly needed. Although Youth Mental Health First Aid (YMHFA) program has been developed to teach the public how to help young people with mental disorders, including depression, it has assumed human altruism and overlooked the possibility that participants would experience conflict between the costs and benefits of helping behaviors. The present qualitative study, therefore, initially explored content of the costs and benefits perceived by youth in terms of helping their peers with depression.

Methods

A total of 56 Japanese undergraduates (32 female, 24 male; Mage = 20.20, SD = 1.09) participated in the face-to-face survey. They were provided with basic knowledge about helping behaviors and were presented with a vignette describing an undergraduate with depression. Then, they left free descriptive comments on their views of the costs/benefits of helping/not helping the person in the vignette. As supplemental quantitative analyses, we statistically compared numbers of labels (n = 624), which were obtained from participants’ comments, across two (costs/benefits) × two (helping/not helping) domains. Finally, we conducted a qualitative content analysis that combined inductive and deductive methods to categorize these labels.

Results

The supplemental quantitative analyses (i.e., ANOVA and post hoc analyses) on the numbers of labels highlighted that the participants perceived suppressors (i.e., costs of helping, benefits of not helping) as well as motivators (i.e., costs of not helping) in making decision to help peers with depression. The qualitative content analysis mainly showed that: (i) the categories in each domain covered multiple facets of costs and benefits, including negative/positive effects on the participants themselves, the person in the vignette, and interpersonal relationships; and that (ii) the participants perceived the conflicts of costs and benefits regardless of whether they help their peers with depression.

Conclusions

These results provide evidence for how young people experience the conflicts between the costs and benefits of helping behaviors toward their peers with depression and reveal specific content of these costs and benefits. These findings could serve as a basis for extending YMHFA programs and designing educational content to promote public helping behaviors in realistic situations.
Care seeking behavior of people with common mental disorders in São Paulo-Brazil
Authors: dos Santos Gustavo de Brito Venâncio , Goldbaum Moisés , César Chester Luiz Galvão , Gianini Reinaldo José
Published: May 2020

Background

Mental health in developing countries is a keen area for improvements. Epidemiological research in this field helps to reinforce information, generate hypothesis and guide police makers. This study intends to analyze patterns of care seeking among cases of common mental disorders (CMD) in São Paulo city in 2015.

Methods

The data is from the population-based survey ISA-Capital 2015 and the screening for common mental disorders follows the Self-reporting questionnaire (SRQ-20). The study analyses care seeking according to sociodemographic and health conditions.

Results

The prevalence of CMD was 19.7% (95% CI 18.2–21.4%). There was a higher prevalence of CMD among who sought care in last 30 days (25.4%). Among CMD cases, care seeking presented significant different prevalence ratio (PR) for: women (PR 1.13; 95% CI 1.05–1.2); age 60 years or more (PR 1.13; 95% CI 1.05–1.22) and 30–44 years (PR 1.10; 95% CI 1.01–1.2); brown skin (PR 0.92; 95% CI 0.86–0.97); single or divorced (PR 0.93; 95% CI 0.89–0.99); unemployed (PR 1.06; 95% CI 1.01–1.12); last 15 days referred morbidity (PR 1.3; 95% CI 1.2–1.34); physical disability (PR 1.11; 95% CI 1.06–1.18); and chronic disease (PR 1.15; 95% CI 1.07–1.24).

Conclusion

Identifying vulnerable groups and developing proper public health actions is important to promote equity accessibility. Analysing care seeking behavior among people with CMD is a strong contribution.
Knockdown of Son, a mouse homologue of the ZTTK syndrome gene, causes neuronal migration defects and dendritic spine abnormalities
Authors: Ueda Masashi , Matsuki Tohru , Fukada Masahide , Eda Shima , Toya Akie , Iio Akio , Tabata Hidenori , Nakayama Atsuo
Published: May 2020

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a rare congenital anomaly syndrome characterized by intellectual disability, brain malformation, facial dysmorphism, musculoskeletal abnormalities, and some visceral malformations is caused by de novo heterozygous mutations of the SON gene. The nuclear protein SON is involved in gene transcription and RNA splicing; however, the roles of SON in neural development remain undetermined. We investigated the effects of Son knockdown on neural development in mice and found that Son knockdown in neural progenitors resulted in defective migration during corticogenesis and reduced spine density on mature cortical neurons. The induction of human wild-type SON expression rescued these neural abnormalities, confirming that the abnormalities were caused by SON insufficiency. We also applied truncated SON proteins encoded by disease-associated mutant SON genes for rescue experiments and found that a truncated SON protein encoded by the most prevalent SON mutant found in ZTTK syndrome rescued the neural abnormalities while another much shorter mutant SON protein did not. These data indicate that SON insufficiency causes neuronal migration defects and dendritic spine abnormalities, which seem neuropathological bases of the neural symptoms of ZTTK syndrome. In addition, the results support that the neural abnormalities in ZTTK syndrome are caused by SON haploinsufficiency independent of the types of mutation that results in functional or dysfunctional proteins.
Biomarker-driven management strategies for peripheral T cell lymphoma
Authors: Mulvey Erin , Ruan Jia
Published: May 2020

Peripheral T cell lymphomas are heterogeneous diseases which remain treatment challenges. Recent advances in molecular and genomic profiling have provided unprecedented insight into disease pathogenesis driven by distinct cells of origins and molecular pathways. The discovery and clinical application of molecular biomarkers in PTCL subtypes has the potential to transform personalized care for patients with PTCL in diagnosis, prognosis, and therapy. Targeting CD30+ PTCL with the antibody-drug conjugate brentuximab vedotin in the relapsed setting and in combination with chemotherapy in the frontline setting has improved patient survivals. Epigenetic modifying agents, including HDAC inhibitors and hypomethylating agents, have demonstrated broad clinical efficacy and durability and are in clinical development for combination strategies for both relapsed and frontline settings. Wide-ranging novel agents targeting critical intracellular pathways and tumor microenvironment are in active exploration to define clinical activities. This review summarizes PTCL-specific biomarkers which are increasingly incorporated in clinical practice to guide precision diagnosis and personalized treatment.
TFEB-NF-κB inflammatory signaling axis: a novel therapeutic pathway of Dihydrotanshinone I in doxorubicin-induced cardiotoxicity
Authors: Wang Xiaoping , Wang Qiyan , Li Weili , Zhang Qian , Jiang Yanyan , Guo Dongqing , Sun Xiaoqian , Lu Wenji , Li Chun , Wang Yong
Published: May 2020

Background

Doxorubicin is effective in a variety of solid and hematological malignancies. Unfortunately, clinical application of doxorubicin is limited due to a cumulative dose-dependent cardiotoxicity. Dihydrotanshinone I (DHT) is a natural product from Salvia miltiorrhiza Bunge with multiple anti-tumor activity and anti-inflammation effects. However, its anti-doxorubicin-induced cardiotoxicity (DIC) effect, either in vivo or in vitro, has not been elucidated yet. This study aims to explore the anti-inflammation effects of DHT against DIC, and to elucidate the potential regulatory mechanism.

Methods

Effects of DHT on DIC were assessed in zebrafish, C57BL/6 mice and H9C2 cardiomyocytes. Echocardiography, histological examination, flow cytometry, immunochemistry and immunofluorescence were utilized to evaluate cardio-protective effects and anti-inflammation effects. mTOR agonist and lentivirus vector carrying GFP-TFEB were applied to explore the regulatory signaling pathway.

Results

DHT improved cardiac function via inhibiting the activation of M1 macrophages and the excessive release of pro-inflammatory cytokines both in vivo and in vitro. The activation and nuclear localization of NF-κB were suppressed by DHT, and the effect was abolished by mTOR agonist with concomitant reduced expression of nuclear TFEB. Furthermore, reduced expression of nuclear TFEB is accompanied by up-regulated phosphorylation of IKKα/β and NF-κB, while TFEB overexpression reversed these changes. Intriguingly, DHT could upregulate nuclear expression of TFEB and reduce expressions of p-IKKα/β and p-NF-κB.

Conclusions

Our results demonstrated that DHT can be applied as a novel cardioprotective compound in the anti-inflammation management of DIC via mTOR-TFEB-NF-κB signaling pathway. The current study implicates TFEB-IKK-NF-κB signaling axis as a previously undescribed, druggable pathway for DIC.
Clinical outcomes of extracorporeal membrane oxygenation in acute traumatic lung injury: a retrospective study
Authors: Lee Hong Kyu , Kim Hyoung Soo , Ha Sang Ook , Park Sunghoon , Lee Hee Sung , Lee Soo Kyung , Lee Sun Hee
Published: May 2020

Background

Therapeutic extracorporeal membrane oxygenation (ECMO) is a challenging procedure in patients who have experienced severe trauma. Particularly, patients with traumatic lung injury and posttraumatic acute respiratory distress syndrome (ARDS) have a high risk of bleeding during this procedure. This study aimed to determine the safety and feasibility of ECMO in patients with traumatic ARDS.

Methods

We retrospectively reviewed medical records and investigated the clinical outcomes of ECMO in 42 patients with traumatic ARDS, among whom near-drowning (42.9%) was the most frequent cause of injury.

Results

Thirty-four of 42 patients (81%) survived and were discharged after a median hospital stay of 23 days. A multivariate analysis identified a lactate level (odds ratio: 1.493, 95% confidence interval: 1.060–2.103, P = 0.022) and veno-venous (VV) ECMO (odds ratio: 0.075, 95% confidence interval: 0.006–0.901, P = 0.041) as favorable independent predictors of survival in patients with traumatic ARDS who underwent ECMO. The optimal cut off value for pre-ECMO lactate level was 10.5 mmol/L (area under the curve = 0.929, P = 0.001). In Kaplan-Meier analysis, the survival rate at hospital discharge was significant higher among the patients with a pre-ECMO lactate level of 10.5 mmol/L or less compared with patients with pre-ECMO lactate level greater than 10.5 mmol/L (93.8% versus 40.0%, respectively; P = 0.01).

Conclusions

ECMO yielded excellent survival outcomes, particularly in patients with low pre-treatment lactate levels who received VV ECMO. Therefore, ECMO appears safe and highly feasible in a carefully selected population of trauma patients.
Possible advantages of early stabilization of spinal fractures in multiply injured patients with leading thoracic trauma - analysis based on the TraumaRegister DGU®
Authors:   TraumaRegister DGU®, Hager Sven , Eberbach Helge , Lefering Rolf , Hammer Thorsten O. , Kubosch David , Jäger Christoph , Südkamp Norbert P. , Bayer Jörg
Published: May 2020

Background

Major trauma often comprises fractures of the thoracolumbar spine and these are often accompanied by relevant thoracic trauma. Major complications can be ascribed to substantial simultaneous trauma to the chest and concomitant immobilization due to spinal instability, pain or neurological dysfunction, impairing the respiratory system individually and together. Thus, we proposed that an early stabilization of thoracolumbar spine fractures will result in significant benefits regarding respiratory organ function, multiple organ failure and length of ICU / hospital stay.

Methods

Patients documented in the TraumaRegister DGU®, aged ≥16 years, ISS ≥ 16, AISThorax ≥ 3 with a concomitant thoracic and / or lumbar spine injury severity (AISSpine) ≥ 3 were analyzed. Penetrating injuries and severe injuries to head, abdomen or extremities (AIS ≥ 3) led to patient exclusion. Groups with fractures of the lumbar (LS) or thoracic spine (TS) were formed according to the severity of spinal trauma (AISspine): AISLS = 3, AISLS = 4–5, AISTS = 3 and AISTS = 4–5, respectively.

Results

1740 patients remained for analysis, with 1338 (76.9%) undergoing spinal surgery within their hospital stay. 976 (72.9%) had spine surgery within the first 72 h, 362 (27.1%) later on. Patients with injuries to the thoracic spine (AISTS = 3) or lumbar spine (AISLS = 3) significantly benefit from early surgical intervention concerning ventilation time (AISLS = 3 only), ARDS, multiple organ failure, sepsis rate (AISTS = 3 only), length of stay in the intensive care unit and length of hospital stay. In multiple injured patients with at least severe thoracic spine trauma (AISTS ≥ 4) early surgery showed a significantly shorter ventilation time, decreased sepsis rate as well as shorter time spend in the ICU and in hospital.

Conclusions

Multiply injured patients with at least serious thoracic trauma (AISThorax ≥ 3) and accompanying spine trauma can significantly benefit from early spine stabilization within the first 72 h after hospital admission. Based on the presented data, primary spine surgery within 72 h for fracture stabilization in multiply injured patients with leading thoracic trauma, especially in patients suffering from fractures of the thoracic spine, seems to be beneficial.
Identification of novel biomarkers for neonatal hypoxic-ischemic encephalopathy using iTRAQ
Authors: Zhu Yuanyuan , Yun Yajing , Jin Meifang , Li Gen , Li Hong , Miao Po , Ding Xin , Feng Xing , Xu Lixiao , Sun Bin
Published: May 2020

Background

A prompt diagnosis of HIE remains a challenge clinically. This study aimed to identify potential biomarkers of neonatal hypoxic-ischemic encephalopathy (HIE) via a novel proteomic approach, the isobaric tags for absolute and relative quantification (iTRAQ) method.

Methods

Blood samples were collected from neonates with mild (n = 4), moderate (n = 4), or severe (n = 4) HIE who were admitted to the neonatal intensive care unit of Children’s Hospital of Soochow University between Oct 2015 and Oct 2017. iTRAQ was performed in HIE patients and healthy controls (n = 4). Bioinformatics analyses including Gene Ontology and KEGG pathway enrichment analysis were performed to evaluate the potential features and capabilities of the identified differentially expressed proteins.

Results

A total of 51 commonly differentially expressed proteins were identified among the comparisons between mild, moderate, and severe HIE as well as healthy controls. Haptoglobin (HP) and S100A8 were most significantly up-regulated in patients with HIE and further validated via real-time PCR and western blotting. The differentially expressed proteins represented multiple biological processes, cellular components and molecular functions and were markedly enriched in complement and coagulation cascades.

Conclusions

HP and S100A8 may serve as a potential biomarker for neonatal HIE and reflects the severity of HIE. The complement and coagulation cascades play crucial roles in the development of neonatal HIE.
Italian pediatric respiratory society recommendations on pediatric pulmonary function testing during COVID-19 pandemic
Authors:   Italian Pediatric Respiratory Society (IPRS) Committee Members, Bignamini Elisabetta , Cazzato Salvatore , Cutrera Renato , Ferrante Giuliana , La Grutta Stefania , Licari Amelia , Lombardi Enrico , Midulla Fabio , Piacentini Giorgio , Pifferi Massimo , Santamaria Francesca , Tancredi Giancarlo , Turchetta Attilio
Published: May 2020

Background

Effective prevention and control strategies are mandatory to prevent SARS-CoV-2 infection.

Main text

The Italian Pediatric Respiratory Society promotes a series of new recommendations that should be followed in pulmonary function testing laboratories during the COVID-19 pandemic.

Conclusion

Pulmonary function testing should be performed in children with chronic lung disease only if it is needed to guide management and limited to the necessary tests, namely spirometry. When performed, strict infection control measures should be followed due to the potential risk of transmitting SARS-CoV-2.
The psycho-social effects of COVID-19 on Italian adolescents’ attitudes and behaviors
Authors: Buzzi Carlo , Tucci Maurizio , Ciprandi Riccardo , Brambilla Ilaria , Caimmi Silvia , Ciprandi Giorgio , Marseglia Gian Luigi
Published: May 2020

Background

COVID-19 is an emerging issue that has significant consequences on psycho-social well-being.

Methods

In this regard, a survey was conducted on a large group of adolescents in Italy. The survey investigated four items: concerns and fears, information on the pandemic, provisions of public authorities (e.g., lockdown), and impact on everyday life.

Results

Adolescents actively participated in the survey. COVID-19 affected emotions and lifestyle. COVID-19 influenced relationships with peers and parents. There were regional differences.

Conclusions

The current research highlighted the remarkable, healthy, and certainly unexpected, emotional balance of the new generations in the face of a sudden, unpredictable phenomenon capable of jeopardizing life itself. While understanding the gravity of the phenomenon and willingly adapting to all the necessary precautions, the adolescents still seemed to express an excellent ability to manage situations of insecurity and to deal with unfavorable and adverse conditions by adapting to the new routine and finding alternative and innovative means of meeting their social and psychological needs.
Association between maternal HIV infection and birthweight in a tertiary hospital in southern Ethiopia: retrospective cohort study
Authors: Zenebe Andualem , Eshetu Betelhem , Gebremedhin Samson
Published: May 2020

Background

Human Immunodeficiency Virus (HIV) infection and low birth weight (LBW) continue to be significant public health concerns in many low-income countries including Ethiopia. Yet the effect of maternal HIV infection on birth weight has not been thoroughly explored and the existing studies reported opposing findings. We examined the association between maternal HIV infection and LBW in a tertiary hospital in Southern Ethiopia.

Methods

A retrospective cohort study was conducted based on the medical records of 277 HIV-negative and 252 HIV-positive mothers who gave singleton live birth between September 2014 to August 2017 in Hawassa University Comprehensive Specialized Hospital, Southern Ethiopia. The recodes were identified using systematic sampling approach and relevant information were extracted by using pretested extraction form. Multivariable binary logit model was fitted to examine the relationship between the exposure and outcome while adjusting for potential confounders. Adjusted odds ratio (AOR) and 95% confidence intervals (CI) is used for summarizing the findings of the analysis.

Results

The mean (± standard deviation) birth weight of infants born to HIV-negative women (3.1 ± 0.7 kg) was significantly higher than those born to HIV-positive counterparts (3.0 ± 0.6 kg) (p = 0.020). The prevalence of LBW was also significantly higher in the HIV-exposed group (22.2%) than the non-exposed group (13.7%) (p = 0.011). In the logit model adjusted for multiple covariates, HIV-positive women had four times increased odds than HIV-negative women to give birth to LBW infant(AOR = 4.03, 95% CI: 2.01–8.06). Other significant predictors of LBW were rural place of residence (AOR = 2.04, 95% CI: 1.16–3.60), prenatal anemia (AOR = 3.17, 95% CI: 1.71–5.90), chronic hypertension (AOR = 3.68, 95% CI: 1.10–12.46) and preeclampsia (AOR = 6.80, 95% CI: 3.00–15.38).

Conclusion

Maternal HIV infection is associated with increased odds of LBW. HIV prevention activities are also likely to contribute for the reduction of LBW.
A randomized controlled study of immediate versus delayed umbilical cord clamping in infants born by elective caesarean section
Authors: De Bernardo Giuseppe , Giordano Maurizio , De Santis Rita , Castelli Paola , Sordino Desiree , Trevisanuto Daniele , Buonocore Giuseppe , Perrone Serafina
Published: May 2020

Background

Delayed umbilical cord clamping is associated with greater haemoglobin concentration and iron storage between 3 and 6 months of life and with less need of blood transfusion and lower incidence of neonatal hypotension compared to early umbilical cord clamping.

Methods

The aim was to test the hypothesis that delayed cord clamping is better than early cord clamping in term infants born by elective caesarean section. Group A was subjected to immediate cord clamping while in the Group B, the umbilical cord was clamped 1 min after birth. Primary aim was revealed the difference in pre-ductal saturation between two groups while secondary aim was investigating the difference in HR, Ht, bilirubin and glycaemia. Pre-ductal SpO2 and HR were recorded at 5 and 10 min after birth, T was analysed 10 min after birth, glycaemia was revealed at 120 min while Ht and bilirubin were collected at 72 h.

Results

132 newborns were enrolled in the study and allocated in ratio 1:1 to group A or B. Delayed cord clamping did not improve SpO2, HR and T values compared to immediate cord clamping (p > 0,05). However, Group B showed greater haematocrit and bilirubin values at 72 h compared to Group A (56,71 ± 6663 vs 51,56 ± 6929; p < 0,05 and 8,54 ± 2,90 vs 7,06 ± 2,76; p < 0,05). Glycaemia value did not differ between two groups (p > 0,05).

Conclusions

Group B did not reveal any differences in SpO2, HR, T and glycaemia compared to Group A. Group B showed greater values of haematocrit and bilirubin but without need of phototherapy.

Trial registration

Umbilical Cord Clamping: What Are the Benefits; NCT03878602. Registered 18 March 2019 retrospectively registered.
Neonatal ten-year retrospective study on neural tube defects in a second level University Hospital
Authors: Piro Ettore , Serra Gregorio , Schierz Ingrid Anne Mandy , Giuffrè Mario , Corsello Giovanni
Published: May 2020

Background

Aim of this retrospective study was to describe clinical characteristics, diagnostic work-up, management and follow-up of newborns with neural tube defects (NTDs), admitted to the Mother and Child Department of the University Hospital of Palermo, in a ten years period.

Methods

The medical records of 7 newborns (5 males and 2 females) admitted, over a 10-year period from January 2010 to March 2020, to our Department on the first day of life were reviewed. Analyzed data were related to familiar and/or maternal risk factors (consanguinity, maternal preexisting and/or gestational diseases, exposure to teratogen/infectious agents, lack of preconception folic acid supplement), demographic (ethnicity/origin, residence) and clinical features (eventual use of assisted reproduction techniques, prenatal diagnosis, gestational age, fetal presentation, type of delivery, birth weight, preoperative imaging, antibiotics and analgesics use, description of the surgery intervention, length of hospital stay, comorbidities, complications), and follow-up.

Results

In our sample we observed a wide spectrum of NTDs: 3 newborns had open NTDs, namely myelomeningocele (2 lumbosacral, one of which associated with extradural lipoma, and 1 sacral), and 4 closed ones, including 2 with meningocele (occipital), 1 filar lipoma associated with dermal sinus, and 1 terminal myelocystocele. Our patients were discharged between 8 and 22 days of life.

The neurodevelopmental follow-up showed a favorable outcome for 4 of the 7 patients, and the appearance over time of neurological impairment (motor and/or autonomic) in the newborns with open NTDs.

Conclusions

This study describes familiar and/or maternal risk factors and demographic and clinical features of a single-center series of newborns with NTDs. It may provide a further outline of the actual phenotypic spectrum of these malformations, and new insights into epidemiological aspects and comprehensive management of the patients, including diagnostic work-up and follow-up evaluations.
Growth patterns and associated risk factors of congenital malformations in twins
Authors: Piro Ettore , Schierz Ingrid Anne Mandy , Serra Gregorio , Puccio Giuseppe , Giuffrè Mario , Corsello Giovanni
Published: May 2020

Background

The rate of twinning continues to increase due to the combined effect of a rise in parental age and increased use of assisted reproductive technology. The risk of congenital anomalies in twins is higher than in singletons, but it is less well reported in relation to growth patterns. We focused to the auxological outcome of twin pregnancies when one or both of twins are affected by one or more malformations.

Methods

We conducted a retrospective observational study reviewing the clinical charts of twins admitted in the period between January 2003 and December 2018 at the University Hospital of Palermo. The associations between malformations and anthropometric variables at birth were analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins.

Results

We studied data of 488 neonates (52% females) from 244 pregnancies. The rate of major congenital anomalies was 11%, affecting significantly the smaller twin (p = .00018; Odds ratio 3.21; 95% CI 1.65 6.59). Malformation class distribution was as following: genitourinary (24%), gastrointestinal (20%), cardiovascular (18.5%), musculoskeletal (11%), central nervous system (9%), syndromic (9%), ocular (5.5%) and diaphragmatic hernia (2%). The most predictive value, the Birthweight (BW) difference mean ratio in malformed versus not malformed neonates (− 0.31 vs 0.02;p = .0016) was distributed equally lower than zero in all malformed twins, except for those with congenital heart defects (p = .0000083).

Microcephaly (head circumference < 2 standard deviation, SD) was present in 3% of symmetrically smaller twin, and severe microcephaly (< 3 SD) was present in 0.6%. We found that an intertwin BW discordance of 18% or greater identified 50% of neonates with microcephaly, but only 11% of malformed twins.

Conclusions

In case of one twin with a BW < 10th centile, a concomitant intertwin BW discordance ≥18% could reveal an increased risk for microcephaly but not for malformation. Lower values of BW, Ponderal index, Body mass index but above all negative value of BW difference mean ratio are associated with malformations in twin pairs.
Effect of mechanical power on intensive care mortality in ARDS patients
Authors: Coppola Silvia , Caccioppola Alessio , Froio Sara , Formenti Paolo , De Giorgis Valentina , Galanti Valentina , Consonni Dario , Chiumello Davide
Published: May 2020

Background

In ARDS patients, mechanical ventilation should minimize ventilator-induced lung injury. The mechanical power which is the energy per unit time released to the respiratory system according to the applied tidal volume, PEEP, respiratory rate, and flow should reflect the ventilator-induced lung injury. However, similar levels of mechanical power applied in different lung sizes could be associated to different effects. The aim of this study was to assess the role both of the mechanical power and of the transpulmonary mechanical power, normalized to predicted body weight, respiratory system compliance, lung volume, and amount of aerated tissue on intensive care mortality.

Methods

Retrospective analysis of ARDS patients previously enrolled in seven published studies. All patients were sedated, paralyzed, and mechanically ventilated.

After 20 min from a recruitment maneuver, partitioned respiratory mechanics measurements and blood gas analyses were performed with a PEEP of 5 cmH2O while the remaining setting was maintained unchanged from the baseline. A whole lung CT scan at 5 cmH2O of PEEP was performed to estimate the lung gas volume and the amount of well-inflated tissue.

Univariate and multivariable Poisson regression models with robust standard error were used to calculate risk ratios and 95% confidence intervals of ICU mortality.

Results

Two hundred twenty-two ARDS patients were included; 88 (40%) died in ICU. Mechanical power was not different between survivors and non-survivors 14.97 [11.51–18.44] vs. 15.46 [12.33–21.45] J/min and did not affect intensive care mortality. The multivariable robust regression models showed that the mechanical power normalized to well-inflated tissue (RR 2.69 [95% CI 1.10–6.56], p = 0.029) and the mechanical power normalized to respiratory system compliance (RR 1.79 [95% CI 1.16–2.76], p = 0.008) were independently associated with intensive care mortality after adjusting for age, SAPS II, and ARDS severity. Also, transpulmonary mechanical power normalized to respiratory system compliance and to well-inflated tissue significantly increased intensive care mortality (RR 1.74 [1.11–2.70], p = 0.015; RR 3.01 [1.15–7.91], p = 0.025).

Conclusions

In our ARDS population, there is not a causal relationship between the mechanical power itself and mortality, while mechanical power normalized to the compliance or to the amount of well-aerated tissue is independently associated to the intensive care mortality. Further studies are needed to confirm this data.
Towards a fasting-mimicking diet for critically ill patients: the pilot randomized crossover ICU-FM-1 study
Authors: Van Dyck Lisa , Vanhorebeek Ilse , Wilmer Alexander , Schrijvers An , Derese Inge , Mebis Liese , Wouters Pieter J. , Van den Berghe Greet , Gunst Jan , Casaer Michaël P.
Published: May 2020

Background

In two recent randomized controlled trials, withholding parenteral nutrition early in critical illness improved outcome as compared to early up-to-calculated-target nutrition, which may be explained by beneficial effects of fasting. Outside critical care, fasting-mimicking diets were found to maintain fasting-induced benefits while avoiding prolonged starvation. It is unclear whether critically ill patients can develop a fasting response after a short-term nutrient interruption. In this randomized crossover pilot study, we investigated whether 12-h nutrient interruption initiates a metabolic fasting response in prolonged critically ill patients. As a secondary objective, we studied the feasibility of monitoring autophagy in blood samples.

Methods

In a single-center study in 70 prolonged critically ill patients, 12-h up-to-calculated-target feeding was alternated with 12-h fasting on day 8 ± 1 in ICU, in random order. Blood samples were obtained at the start of the study, at the crossover point, and at the end of the 24-h study period. Primary endpoints were a fasting-induced increase in serum bilirubin and decrease in insulin requirements to maintain normoglycemia. Secondary outcomes included serum insulin-like growth factor I (IGF-I), serum urea, plasma beta-hydroxybutyrate (BOH), and mRNA and protein markers of autophagy in whole blood and isolated white blood cells. To obtain a healthy reference, mRNA and protein markers of autophagy were assessed in whole blood and isolated white blood cells of 23 matched healthy subjects in fed and fasted conditions. Data were analyzed using repeated-measures ANOVA, Fisher’s exact test, or Mann–Whitney U test, as appropriate.

Results

A 12-h nutrient interruption significantly increased serum bilirubin and BOH and decreased insulin requirements and serum IGF-I (all p ≤ 0.001). Urea was not affected. BOH was already increased from 4 h fasting onwards. Autophagic markers in blood samples were largely unaffected by fasting in patients and healthy subjects.

Conclusions

A 12-h nutrient interruption initiated a metabolic fasting response in prolonged critically ill patients, which opens perspectives for the development of a fasting-mimicking diet. Blood samples may not be a good readout of autophagy at the tissue level.

Trial registration

ISRCTN, ISRCTN98404761. Registered 3 May 2017.
Comparison of the therapeutic effects of 15 mg and 30 mg initial dosage of prednisolone daily in patients with subacute thyroiditis: protocol for a multicenter, randomized, open, parallel control study
Authors: Xu Shaoyong , Jiang Yuxin , Jia Aihua , Zhang Juan , Gao Bin , Xu Jing , Jing Xiaorui , Jiao Yang , Wei Jia , Xu Wenlei , Chen Ruikun , Gao Ling , Shang Lei
Published: May 2020

Background

Subacute thyroiditis (SAT) is the most common cause of thyroid pain. Several clinical guidelines recommend that patients who fail to respond to full doses of non-steroidal anti-inflammatory drugs (NSAIDs) should be treated instead with oral corticosteroid therapy. However, albeit strong recommendations, the treatment protocol is based on low-quality evidence and high-quality clinical trials are lacking with respect to the optimal initiation dosage and usage of corticosteroid. We aimed to evaluate whether 15 mg/day of prednisolone (PSL) as the initial dosage could provide non-inferiority effectiveness but with lower risk and more safety compared with 30 mg/day of PSL as the initial dosage.

Methods/design

This is a multicenter, open-label, randomized, parallel trial that will be conducted at five academic hospitals in China. A total of 90 adult patients diagnosed with SAT who present moderate to severe pain or fail to respond to full doses of NSAIDs will be randomly assigned with a 1:1 ratio to the low initial PSL dosage group (15 mg daily) and standard initial PSL dosage group (30 mg daily). The primary endpoint is the time period (days) required for PSL treatment (including PSL treatment for recurrence).

Discussion

Our randomized controlled trial will try to determine the optimal protocol in the treatment of SAT by providing high-quality evidence.

Trials registration

Chinese Clinical Trial Register, ChiCTR1900023884. Registered on 15 June 2019.