bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of informal family care during acute hospitalization of older adults from different ethno-cultural groups in Israel
Authors: Shulyaev Ksenya , Gur-Yaish Nurit , Shadmi Efrat , Zisberg Anna
Published: November 2020

Introduction

Informal caregiving during hospitalization of older adults is significantly related to hospital processes and patient outcomes. Studies in home settings demonstrate that ethno-cultural background is related to various aspects of informal caregiving; however, this association in the hospital setting is insufficiently researched.

Objectives

Our study explore potential differences between ethno-cultural groups in the amount and kind of informal support they provide for older adults during hospitalization.

Methods

This research is a secondary data analysis of two cohort studies conducted in Israeli hospitals. Hospitalized older adults are divided into three groups: Israeli-born and veteran immigrant Jews, Arabs, and Jewish immigrants from the Former Soviet Union (FSU). Duration of caregiver visit, presence in hospital during night hours, type of support (using the Informal Caregiving for Hospitalized Older Adults scale) are assessed during hospitalization. Results are controlled by background parameters including functional Modified Barthel Index (MBI) and cognitive Short Portable Mental Status Questionnaire (SPMSQ) status, chronic morbidity (Charlson), and demographic characteristics.

Results

Informal caregivers of “FSU immigrants” stay fewer hours during the day in both cohorts, and provide less supervision of medical care in Study 2, than caregivers in the two other groups. Findings from Study 1 also suggest that informal caregivers of “Arab” older adults are more likely to stay during the night than caregivers in the two other groups.

Conclusions

Ethno-cultural groups differ in their patterns of caregiving of older adults during hospitalization. Health care professionals should be aware of these patterns and the cultural norms that are related to caregiving practices for better cooperation between informal and formal caregivers of older adults.
Social inequalities in breast cancer screening: evaluating written communications with immigrant Haitian women in Montreal
Authors: Raynault Marie-France , Féthière Christelle , Côté Dominique
Published: November 2020

Background

The province of Quebec (Canada) has implemented a breast cancer screening program to diagnose this cancer at an early stage. The strategy is to refer women 50 to 69 years old for a mammogram every two years by sending an invitation letter that acts as a prescription. Ninety per cent (90%) of deaths due to breast cancer occur in women aged 50 and over. Numerous studies have shown social inequalities in health for most diseases. With breast cancer, a significant paradox arises: its incidence is lower among disadvantaged women and yet, more of them die from this disease. The health care system might play a role in this inequality. The scientific literature documents the potential for creating such inequalities when prevention does not consider equity among social groups. Immigrant women are often disadvantaged. They die of breast cancer more than non-immigrants. Studies attribute this to late-stage diagnosis due to poor adherence to mammography screening programs.

Purpose of the study

The main objective of our research is to assess how Haitian immigrant women in Montreal are reached by the Quebec Breast Cancer Screening Program, and specifically how they perceive the mammogram referral letter sent by the program.

Methods

The study uses a two-step qualitative method:i)In-depth interviews with influential community workers to identify the most relevant issues;ii)Focus groups with disadvantaged women from Montreal’s Haitian community.

Results

A mammogram referral letter from the Breast Cancer Screening Program may be a barrier to compliance with mammography by underprivileged Haitian women in Montreal. This might be attributable to a low level of literacy, poor knowledge of the disease, and lack of financial resources.

Conclusion

Barriers may be underestimated in underprivileged immigrant and non-immigrant communities. A preventive strategy must be adapted to different sub-groups and must also take into account lower literacy levels. To increase mammography uptake, it is crucial that the benefits of prevention be clearly identified and described in understandable terms. Finally, economic access to follow-up measures should be considered.
The use of a bed with an insulating system of electromagnetic fields improves immune function, redox and inflammatory states, and decrease the rate of aging
Authors: Díaz-Del Cerro E. , Vida C. , Martínez de Toda I. , Félix J. , De la Fuente M.
Published: November 2020

Background

The immune system, as a homeostatic system, is an excellent marker of health and has also been proposed as an indicator of the rate of aging. The base of the age-related changes in the immune system, “immunosenescence”, is oxidative-inflammatory stress. Studies have shown that long-term exposure to electromagnetic fields (EMFs) produced by technology causes inhibitory effects on the immune response and increases oxidation. The aim of the present study was to investigate the effects of resting on an EMF-insulated system on several immune functions, the oxidative-inflammatory state and subsequently the rate of aging (biological age).

Methods

Several immune functions, in peripheral blood neutrophils and mononuclear cells, of 31 volunteers were analyzed before and after 2 months of using a bed with the patented HOGO system, which insulated participants against EMFs. Several oxidative and inflammatory parameters, in whole blood cells, were also studied. The biological age was calculated using a mathematical formula, which was based on several immune function parameters. A placebo group of 11 people using beds without that property were used as a control.

Results

The results showed a significant improvement of immune functions and antioxidant and anti-inflammatory defenses after using the HOGO system for 2 months. In addition, a decrease in oxidants and pro-inflammatory compounds, a lowering of oxidative damage in lipids and in DNA as well as a reduction of calculated biological age was also observed. The placebo group did not show any changes.

Conclusions

In conclusion, 2 months of resting on a bed insulated from EMFs demonstrates improvement in immune function, oxidative-inflammatory state and biological age.
Mortality in Yusho patients exposed to polychlorinated biphenyls and polychlorinated dibenzofurans: a 50-year retrospective cohort study
Authors: Onozuka Daisuke , Nakamura Yuko , Tsuji Gaku , Furue Masutaka
Published: November 2020

Background

In 1968, the Yusho incident resulted in accidental exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related compounds in Japan. This study updated the risk of mortality in Yusho patients.

Methods

We obtained updated cohort data for all Yusho patients for the period 1968–2017. We calculated standardized mortality ratios (SMRs) for all-cause and cause-specific mortality over a 50-year follow-up period compared with the general population in Japan.

Results

A total of 1664 Yusho patients with 63,566 person-years of follow up were included in the analysis. Among males, excess mortality was observed for all cancers (SMR: 1.22, 95% confidence interval [CI]: 1.02 to 1.45) and lung cancer (SMR: 1.59, 95% CI: 1.12 to 2.19). Among females, increased mortality was observed for liver cancer (SMR: 2.05, 95% CI: 1.02 to 3.67). No significant increase was seen in non-cancer-related mortality compared with the general population.

Conclusions

Carcinogenic risk in humans after exposure to PCBs and PCDFs remains higher among Yusho patients. Our findings suggest the importance of care engagement and optimum management to deal with the burden of Yusho disease.
Association of dietary pattern and physical activity with lipid-related indices among Chinese population: a cross-sectional study
Authors: Guo Qiao , Ma Zuchang , Zhu Changan , Zeng Qiang
Published: November 2020

Background and objectives

To explore the relationship between dietary patterns, physical activity and lipid-related indices in Chinese Population.

Methods and study design

This study included 21,472 (72.3% men) participants aged 16 to 78 years. Data of anthropometric measurements, biochemical tests and questionnaires were collected through a physical examination. Diet patterns were identified through factor analysis and five patterns were retained (“meat,” “high-energy,” “high-protein,” “healthy” and “traditional Chinese”). Physical activity was classified into low, moderate, or high. Abnormalities in lipid indices were assessed using the Adult Treatment Panel III criterion.

Results

Higher factor scores of “high-protein” pattern and “healthy” pattern were found to be related to favorable lipid indices. Quartiles 3 and 4 of “meat” pattern showed increased risks of having elevates total cholesterol and low-density lipoprotein cholesterol concentrations. Participants with higher levels of physical activity showed lowest risk of abnormal lipid profiles. All the associations were equally established among men, while most were no longer significant among women.

Conclusions

Higher physical activity level and a dietary pattern consists of high-quality protein foods, vegetables and fruits were associated with favorable lipid profiles, and these lifestyle factors were related to the risk of dyslipidemia in a sex-specific way.
Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects
Authors: Javed Rabia , Zia Muhammad , Naz Sania , Aisida Samson O. , Ain Noor ul , Ao Qiang
Published: November 2020

Capping agents are of utmost importance as stabilizers that inhibit the over-growth of nanoparticles and prevent their aggregation/coagulation in colloidal synthesis. The capping ligands stabilize the interface where nanoparticles interact with their medium of preparation. Specific structural features of nanoparticles are attributed to capping on their surface. These stabilizing agents play a key role in altering the biological activities and environmental perspective. Stearic effects of capping agents adsorbed on the surface of nanoparticles are responsible for such changing physico-chemical and biological characteristics. Firstly, this novel review article introduces few frequently used capping agents in the fabrication of nanoparticles. Next, recent advancements in biomedicine and environmental remediation approaches of capped nanoparticles have been elaborated. Lastly, future directions of the huge impact of capping agents on the biological environment have been summarized.
The effect of methadone on depression among addicts: a systematic review and meta-analysis
Authors: Mohammadi Masoud , Kazeminia Mohsen , Abdoli Nasrin , Khaledipaveh Behnam , Shohaimi Shamarina , Salari Nader , Hosseinian-Far Melika
Published: November 2020

Background

Opioids addiction and misuse are among the major problems in the world today. There have been several preliminary studies examining the effect of methadone on depression among addicts, however, these studies have reported inconsistent and even contradictory results. Therefore, the aim of the present study was to determine the effect of methadone on depression in addicts in Iran and around the world, using a meta-analysis approach.

Methods

This study was a systematic review and meta-analysis including articles published in the SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science databases were searched systematically to find articles published from 2006 to March 2019. Heterogeneity index was determined using the Cochran's test (Qc) and I2. Considering heterogeneity of studies, the random effects model was used to estimate the standardized difference of mean score for depression. Subsequently, the level of depression reduction in Iran and worldwide in the intervention group before and after the testwas measured.

Results

A total of 19 articles met the inclusion criteria, and were therefore selected for this systematic review and meta-analysis. The sample size of the intervention group in the selected studies was 1948. According to the meta-analysis results, the mean depression score in the intervention group was 26.4 ± 5.6 and 18.4 ± 2.6 before and after intervention respectively, indicating the reducing effect of methadone on depression, and this difference was statistically significant (P < 0.01).

Conclusion

The results of the present study show that methadone significantly reduces depression in addicts. Therefore, regular methadone use can be part of a drug treatment plan.
Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature
Authors: Ma Wei , Zhao Fangkun , Yu Xinmiao , Guan Shu , Suo Huandan , Tao Zuo , Qiu Yue , Wu Yunfei , Cao Yu , Jin Feng
Published: November 2020

Background

Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer.

Methods

We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan–Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses.

Results

A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p = 1.215e − 06 in the training set; p = 0.0069 in the validation set; p = 1.233e − 07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR = 1.432; 95% CI 1.204–1.702, p < 0.001), validation set (HR = 1.162; 95% CI 1.004–1.345, p = 0.044), and whole set (HR = 1.240; 95% CI 1.128–1.362, p < 0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways.

Conclusions

We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.
Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients
Authors: Hwang Ilseon , Kim Jeong Won , Ylaya Kris , Chung Eun Joo , Kitano Haruhisa , Perry Candice , Hanaoka Jun , Fukuoka Junya , Chung Joon-Yong , Hewitt Stephen M.
Published: November 2020

Background

The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC).

Methods

Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system.

Results

CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p < 0.001). Furthermore, elevated M2 ratio (CD163+/CD68+) was significantly associated with poor overall survival (p = 0.023). Dual expression of M2 ratiohigh and VEGF-Chigh (M2 ratiohighVEGF-Chigh) was correlated with worse overall survival (p = 0.033). Multivariate analysis revealed that M2 ratiohigh [HR (95% CI) = 1.53 (1.01–2.33), p = 0.046] and combined M2 ratiohighVEGF-Chigh expression [HR (95% CI) = 2.01 (1.28–3.16), p = 0.003] were independent predictors of poor overall survival. Notably, we confirmed that M2 macrophages significantly enhanced the protein and mRNA expression of both VEGF-A and VEGF-C, while M1 macrophages induced only mRNA expression of VEGF-A in A549 cells.

Conclusions

This study suggests that TAMs are significantly associated with angiogenesis and lymphangiogenesis, contributing to the progression of NSCLC. Furthermore, elevated M2 ratio, similar to combined high M2 ratio and high VEGF-C expression, is a strong indicator of poor prognosis in patients with NSCLC, providing insight for future TAM-based immunotherapy strategies.
Characterization of speed adaptation while walking on an omnidirectional treadmill
Authors: Soni Smit , Lamontagne Anouk
Published: November 2020

Background

Conventional treadmills are widely used for gait retraining in rehabilitation setting. Their usefulness for training more complex locomotor tasks, however, remains limited given that they do not allow changing the speed nor the direction of walking which are essential walking adaptations for efficient and safe community ambulation. These drawbacks can be addressed by using a self-pace omnidirectional treadmill, as those recently developed by the gaming industry, which allows speed changes and locomotor movements in any direction. The extent to which these treadmills yield a walking pattern that is similar to overground walking, however, is yet to be determined.

Methods

The objective of this study was to compare spatiotemporal parameters, body kinematics and lower limb muscle activation of healthy young individuals walking at different speeds (slow, comfortable, fast) on a low-cost non-motorized omnidirectional treadmill with and without virtual reality (VR) vs. overground.

Results

Results obtained from 12 young healthy individuals (18–29 years) showed that participants achieved slower speed on the treadmill compared to overground. On the treadmill, faster walking speeds were achieved by a mere increase in cadence, as opposed to a combined increase in cadence and step length when walking overground. At matched speed, enhanced stance phase knee flexion, reduced late stance ankle plantarflexion, as well as enhanced activation amplitudes of hip extensors in late stance and hip extensors in early swing were observed. The addition of VR to treadmill walking had little or no effect of walking outcomes. Collectively, results show that the omnidirectional treadmill yields a different walking pattern and lead to different adaptations to speed compared to overground walking. We suggest that these alterations are mainly driven by the reduced shear forces between the weight bearing foot and supporting surface and a perceived threat to balance on the omnidirectional treadmill.

Conclusion

Since such treadmills are likely to be used for prolonged periods of time by gamers or patients undergoing physical rehabilitation, further research should aim at determining the impact of repeated exposure on gait biomechanics and lower limb musculoskeletal integrity.
Self-efficacy, support and sustainability – a qualitative study of the experience of establishing breastfeeding for first-time Australian mothers following early discharge
Authors: James Lucy , Sweet Linda , Donnellan-Fernandez Roslyn
Published: November 2020

Background

Ensuring women receive optimal breastfeeding support is of key importance to the health of mothers and their infants. Early discharge within 24 h of birth is increasingly common across Australia, and the practice of postnatal home visiting varies between settings. The reduction in length of stay without expansion of home visits reduces midwives’ ability to support breastfeeding. The impact of early discharge on first-time mothers establishing breastfeeding was unknown. The study aim was to understand the experiences of first-time Australian mothers establishing breastfeeding when discharged from the hospital within 24 h of a normal vaginal birth.

Methods

A qualitative interpretive method was used. Semi-structured interviews with 12 women following early discharge were conducted. Data were audio recorded, professionally transcribed, and subjected to a thematic analysis.

Results

Three interconnected themes of ‘self-efficacy’, ‘support’ and ‘sustainability’ were identified. Self-efficacy influenced the women’s readiness and motivation to be discharged home early and played a role in how some of the mothers overcame breastfeeding challenges. Social, semi-professional and professional breastfeeding supports were key in women’s experiences. Sustainability referred to and describes what women valued in relation to continuation of their breastfeeding journey.

Conclusion

This study found accessible people-based breastfeeding services in the community are valued following early discharge. Furthermore, there is demand for more evidence-based breastfeeding educational resources, potentially in the form of interactive applications or websites. Additionally, a focus on holistic and individualised breastfeeding assessment and care plans prior to discharge that link women with ongoing breastfeeding services is paramount.
Recommendation regarding the cranial upper border of level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma
Authors: Wang Lijun , Huang Shengfu , Zhang Lanfang , He Xia , Liu Yatian
Published: November 2020

Purpose

To recommend a cranial border for level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy and to help reach a consensus on contouring level IIb in CTV.

Methods

From 2012 to 2016, 331 nonmetastatic NPC patients treated with IMRT were retrospectively enrolled. Based on the AJCC 8th staging system of NPC, there were 15 stage I, 76 stage II, 103 stage III, and 137 stage IV patients. The distribution of cervical lymph nodes in NPC was assessed based on imaging. Comparisons of the safety and parotid dose parameters between patients with and without a reduction in the size of level IIb were conducted using SPSS 25.0 and R 2.14.2 software.

Results

Metastasis rates in the most commonly involved lymph nodes, the lateral retropharyngeal and IIb nodes, were 82.8% and 64.0%, respectively. Among patients with level IIb involvement, the upper borders of the metastatic nodes were beyond the caudal edge of C1 in 13.7% of cases. The parotid gland D50 and V26 values were significantly reduced after modifying the upper bound of level IIb used to delineate the CTV (P = 0.000).

Conclusion

In principle, the upper bound of level IIb should reach the lateral skull base during delineation of the cervical CTV for NPC. To protect the parotid glands, however, individualized reduction of the upper bound of level IIb is recommended for patients who meet certain criteria.
The accuracy of a novel pedicle screw insertion technique assisted by a special angular scale in the subaxial cervical spine using lateral mass as a reference marker
Authors: Shi Hang , Zhu Lei , Ma Jun , Zhu Yu-Cheng , Wu Xiao-Tao
Published: November 2020

Background

Posterior cervical pedicle screw (CPS) internal fixation has better biomechanical stability than other posterior cervical fixation methods. However, this technique is limited in clinical practice due to the complex anatomical structure and the adjacent relationship of the cervical pedicle, and the high risk of neurovascular injury. The purpose of this study was to describe a novel subaxial CPS insertion technique assisted by a special angular scale using lateral mass as a reference marker and to evaluate the accuracy of CPS placement and the distribution characteristics of CPS misplacement.

Methods

A total of 36 patients with subaxial cervical spine diseases who underwent posterior CPS fixation were consecutively selected. The optimal entry point on the posterior surface of the lateral mass was identified on the three-dimensional cervical model reconstructed from preoperative computed tomography (CT) images. The pedicle transverse angle (PTA) and pedicle-lateral mass angle (PLMA) were measured on the transverse and sagittal CT images respectively. The pedicle screws were inserted according to the preoperatively planned entry point and angles. We analysed the postoperative CT images for CPS misplacement rates and perforation directions following the Lee classification.

Results

Overall, 177 pedicle screws were inserted, of which 119 (67.2%) were classified as grade 0, 43 (24.3%) as grade 1, 12 (6.8%) as grade 2 and 3 (1.7%) as grade 3 by the postoperative CT images. The accuracy rate of CPS placement was 91.5%. Of the 15 misplaced pedicle screws (grades 2 and 3), 11 were lateral pedicle perforations, 3 were superior perforations and 1 was an inferior perforation. There were no neurovascular injuries related to CPS misplacement.

Conclusions

With our technique, the optimal entry point and two angles (PTA and PLMA) were identified for CPS insertion. The novel CPS insertion technique assisted by a special angular scale provides high accuracy and few complications.
miR-129-3p alleviates chondrocyte apoptosis in knee joint fracture-induced osteoarthritis through CPEB1
Authors: Chen Ruixiong , Ye Baoqing , Xie Han , Huang Yuliang , Wu Zhehui , Wu Hongbo , Wang Xiaofeng , Miao Haixiong , Liang Weiguo
Published: November 2020

Background

Osteoarthritis (OA), a refractory disease, is one of the leading contributors for disability worldwide. Since chondrocyte is the only resident cell in cartilage, this study aims to explore the roles of miR-129-3p and CPEB1 in chondrocyte apoptosis in knee joint fracture-induced OA.

Methods

Cartilage was collected from 20 OA patients who underwent total knee replacement (OA group) and 20 patients with knee contusion (normal group). Then, miR-129-3p and CPEB1 levels in the cartilage were quantified by qRT-PCR. Primary rat chondrocytes in the knee were isolated and identified by toluidine blue staining and immunofluorescent staining of type II collagen. OA cellular models were induced by TNF-α treatment, in which miR-129-3p and CPEB1 expressions were assessed. Subsequently, cell viability, apoptosis, and the expression levels of apoptotic protein and caspase-3 were measured. Dual luciferase reporter assay identified the interaction between miR-129-3p and CPEB1.

Results

Patients in the OA group had decreased miR-129-3p expression and increased CPEB1 expression than those in the normal group. TNF-α treatment successfully induced the OA cellular model. Downregulated miR-129-3p and upregulated CPEB1 expressions were found in OA-treated chondrocytes. miR-129-3p overexpression or CPEB1 knockdown improved chondrocyte viability and attenuated apoptosis, and vice versa. miR-129-3p negatively regulated CPEB1, thus ameliorating apoptosis and enhancing cell viability.

Conclusion

miR-129-3p negatively targeted CPEB1 to facilitate chondrocyte viability and hamper apoptosis.
Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue
Authors: Lemoine L. , Ledreux A. , Mufson E. J. , Perez S. E. , Simic G. , Doran E. , Lott I. , Carroll S. , Bharani K. , Thomas S. , Gilmore A. , Hamlett E. D. , Nordberg A. , Granholm A. C.
Published: November 2020

Introduction

Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers (3H-MK6240 and 3H-THK5117) and one amyloid (3H-PIB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD.

Methods

Tau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo.

Results

The two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3H-THK5117, 3H-MK6240 and 3H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3H-PIB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites.

Conclusions

This study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.
Gross genetic alterations and genetic heterogeneity in a periductal stromal tumor of the breast
Authors: Holzmann Carsten , Helmke Burkhard , Bullerdiek Joern
Published: November 2020

Background

Periductal stromal tumors of the breast are exceedingly rare biphasic breast tumors with close morphological relationship to phyllodes tumors. So far, results of genetic analyses on these tumors have not been reported.

Case presentation

A 50 year old female patient was admitted to the hospital because of a palpable lump in her right breast with a diameter of approximately 5–6 cm which was surgically removed by lumpectomy. Histologic examination revealed a biphasic breast tumor classified as periductal stromal tumor. Array analysis showed a pseudotetraploid tumor with a copy number of 4 for most of the chromosomes. In addition, further changes of chromosomes 1, 5, and 6 were noted but there were no mutations of MED12 as those frequently seen in fibroadenomas or phyllodes tumors.

Conclusions

The genetic alterations observed indicate karyotypic evolution leading to marked heterogeneity which fits with the tumor´s histologic and cytologic appearance as well as with its malignant behavior. Because of the absence of genetic similarities with phyllodes tumors, the case does not offer evidence for a common entity but rather suggests the existence of two independent entities.
Enhanced bodily states of fear facilitates bias perception of fearful faces
Authors: Jung Won-Mo , Lee Ye-Seul , Lee In-Seon , Wallraven Christian , Ryu Yeonhee , Chae Younbyoung
Published: November 2020

We investigated whether enhanced interoceptive bodily states of fear would facilitate recognition of the fearful faces. Participants performed an emotional judgment task after a bodily imagery task inside a functional magnetic resonance imaging scanner. In the bodily imagery task, participants were instructed to imagine feeling the bodily sensations of two specific somatotopic patterns: a fear-associated bodily sensation (FBS) or a disgust-associated bodily sensation (DBS). They were shown faces expressing various levels of fearfulness and disgust and instructed to classify the facial expression as fear or disgust. We found a stronger bias favoring the “fearful face” under the congruent FBS condition than under the incongruent DBS condition. The brain response to fearful versus intermediate faces increased in the fronto-insular-temporal network under the FBS condition, but not the DBS condition. The fearful face elicited activity in the anterior cingulate cortex and extrastriate body area under the FBS condition relative to the DBS condition. Furthermore, functional connectivity between the anterior cingulate cortex/extrastriate body area and the fronto-insular-temporal network was modulated according to the specific bodily sensation. Our findings suggest that somatotopic patterns of bodily sensation provide informative access to the collective visceral state in the fear processing via the fronto-insular-temporal network.
Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain
Authors: Kawamura Atsuki , Abe Yoshifumi , Seki Fumiko , Katayama Yuta , Nishiyama Masaaki , Takata Norio , Tanaka Kenji F. , Okano Hideyuki , Nakayama Keiichi I.
Published: November 2020

CHD8 encodes a chromatin-remodeling factor and is one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Although we have recently shown that mice heterozygous for Chd8 mutation manifest myelination defects and ASD-like behaviors, the detailed mechanisms underlying ASD pathogenesis have remained unclear. Here we performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) in oligodendrocyte lineage-specific Chd8 heterozygous mutant mice. DTI revealed that ablation of Chd8 specifically in oligodendrocytes of mice was associated with microstructural changes of specific brain regions including the cortex and striatum. The extent of these changes in white matter including the corpus callosum and fornix was correlated with total contact time in the reciprocal social interaction test. Analysis with rsfMRI revealed changes in functional brain connectivity in the mutant mice, and the extent of such changes in the cortex, hippocampus, and amygdala was also correlated with the change in social interaction. Our results thus suggest that changes in brain microstructure and functional connectivity induced by oligodendrocyte dysfunction might underlie altered social interaction in mice with oligodendrocyte-specific CHD8 haploinsufficiency.
Roquin1 inhibits the proliferation of breast cancer cells by inducing G1/S cell cycle arrest via selectively destabilizing the mRNAs of cell cycle–promoting genes
Authors: Lu Wenbao , Zhou Meicen , Wang Bing , Liu Xueting , Li Bingwei
Published: November 2020

Background

Dysregulation of cell cycle progression is a common feature of human cancer cells; however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest in breast cancer.

Methods

Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and its association with patient survival. Quantitative real-time PCR and Western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assays, flow cytometry, and in vivo analyses were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA sequencing was applied to identify the differentially expressed genes regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.

Results

We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse-free survival of patients with breast cancer. Roquin1 overexpression inhibited cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizes cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2), by targeting the stem–loop structure in the 3′ untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.

Conclusions

Our findings demonstrated that Roquin1 is a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might be a potential molecular target for breast cancer treatment.
Children with special health care needs attending emergency department in Italy: analysis of 3479 cases
Authors:   on behalf of the Italian Society of Pediatrics (SIP), Cianci Paola ,   the Italian Society of Pediatric Genetic Diseases and Congenital Disabilities (SIMGePed) the Italian Society of Pediatric Emergency Medicine (SIMEUP),   the Italian Society For The Study Of Inborn Metabolic Disorders And Newborn Screening (SIMMENS) and Members of Italian Network, D’Apolito Valeria , Moretti Alex , Barbagallo Massimo , Paci Sabrina , Carbone Maria Teresa , Lubrano Riccardo , Urbino Antonio , Dionisi Vici Carlo , Memo Luigi , Zampino Giuseppe , La Marca Giancarlo , Villani Alberto , Corsello Giovanni , Selicorni Angelo
Published: November 2020

Background

Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements.

Methods

Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals.

Results

Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs.

Conclusions

Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity.
Lung ultrasound in outpatient approach to children with suspected COVID 19
Authors: Gregori Giuseppe , Sacchetti Roberto
Published: November 2020

Background

Children with COVID 19 infection (CV19) generally have a mild disease whose main symptoms are fever and cough. Dyspnoea and hypoxemia are rarely reported and few data are available on the frequency and extent of lung involvement in children with CV19. In addition, due to the limited availability of diagnostic tests in Italy during the pandemic period and the relative reliability of the test results, the diagnostic suspicion of CV19 infection in most of the children was difficult to confirm. The aim of this study is to evaluate if lung ultrasound (LUS) was able to highlight typical interstitial lung lesions in children with persistent cough and suspected CV19, providing corroborating evidence of CV19 infection.

Methods

We retrospectively analysed the data of 32 children who came consecutively to our outpatient observation in the period between March 1st and April 30th, 2020 because of the presence of persistent cough for at least 3 days and with suspected CV19. All the children undergone clinical examination, oximetry measurement and LUS.

Results

Twenty over thirty-two children had US lesions compatible with the presence of CV19, many of them without clinical signs of respiratory distress. LUS is much more sensitive than clinical examination to detect lung injury in children with suspected CV19.

Conclusion

In the absence of reliable, highly sensitive diagnostic tests or when nasal swab is unworkable or there are too many requests to be performed quickly due to the pandemic, LUS should be used in children with persistent cough for whom a CV19 is suspected because it can highlight undiagnosed interstitial lung lesions and reinforce the diagnostic suspicion of CV19 This approach can be very useful in outpatient settings and in areas with limited medical resources such as developing countries.
Nasal high flow higher than 60 L/min in patients with acute hypoxemic respiratory failure: a physiological study
Authors: Basile Maria Cristina , Mauri Tommaso , Spinelli Elena , Dalla Corte Francesca , Montanari Giacomo , Marongiu Ines , Spadaro Savino , Galazzi Alessandro , Grasselli Giacomo , Pesenti Antonio
Published: November 2020

Background

Nasal high flow delivered at flow rates higher than 60 L/min in patients with acute hypoxemic respiratory failure might be associated with improved physiological effects. However, poor comfort might limit feasibility of its clinical use.

Methods

We performed a prospective randomized cross-over physiological study on 12 ICU patients with acute hypoxemic respiratory failure. Patients underwent three steps at the following gas flow: 0.5 L/kg PBW/min, 1 L/kg PBW/min, and 1.5 L/kg PBW/min in random order for 20 min. Temperature and FiO2 remained unchanged. Toward the end of each phase, we collected arterial blood gases, lung volumes, and regional distribution of ventilation assessed by electrical impedance tomography (EIT), and comfort.

Results

In five patients, the etiology was pulmonary; infective disease characterized seven patients; median PaO2/FiO2 at enrollment was 213 [IQR 136–232]. The range of flow rate during NHF 1.5 was 75–120 L/min. PaO2/FiO2 increased with flow, albeit non significantly (p = 0.064), PaCO2 and arterial pH remained stable (p = 0.108 and p = 0.105). Respiratory rate decreased at higher flow rates (p = 0.014). Inhomogeneity of ventilation decreased significantly at higher flows (p = 0.004) and lung volume at end-expiration significantly increased (p = 0.007), but mostly in the non-dependent regions. Comfort was significantly poorer during the step performed at the highest flow (p < 0.001).

Conclusions

NHF delivered at rates higher than 60 L/min in critically ill patients with acute hypoxemic respiratory failure is associated with reduced respiratory rate, increased lung homogeneity, and additional positive pressure effect, but also with worse comfort.
The evolution of relapse of adult T cell acute lymphoblastic leukemia
Authors: Sentís Inés , Gonzalez Santiago , Genescà Eulalia , García-Hernández Violeta , Muiños Ferran , Gonzalez Celia , López-Arribillaga Erika , Gonzalez Jessica , Fernandez-Ibarrondo Lierni , Mularoni Loris , Espinosa Lluís , Bellosillo Beatriz , Ribera Josep-Maria , Bigas Anna , Gonzalez-Perez Abel , Lopez-Bigas Nuria
Published: November 2020

Background

Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases.

Results

We profile whole-genome somatic mutations of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies and analyze their evolution upon treatment in comparison with 238 pediatric and young adult ALL cases. We compare the mutational processes and driver mutations active in primary and relapse adult T-ALLs with those of pediatric patients. A precise estimation of clock-like mutations in leukemic cells shows that the emergence of the relapse clone occurs several months before the diagnosis of the primary T-ALL. Specifically, through the doubling time of the leukemic population, we find that in at least 14 out of the 19 patients, the population of relapse leukemia present at the moment of diagnosis comprises more than one but fewer than 108 blasts. Using simulations, we show that in all patients the relapse appears to be driven by genetic mutations.

Conclusions

The early appearance of a population of leukemic cells with genetic mechanisms of resistance across adult T-ALL cases constitutes a challenge for treatment. Improving early detection of the malignancy is thus key to prevent its relapse.