bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating changes in negative posttrauma cognition as a mechanism of PTSD severity changes in two separate intensive treatment programs for veterans
Authors: Held Philip , Kaysen Debra L. , Smith Dale L.
Published: November 2022

Background

A wealth of evidence has illustrated that reductions in negative posttrauma cognitions (NPCs) predict improvement in posttraumatic stress disorder (PTSD) symptoms during treatment. Yet, the specific temporal arrangement of changes in these constructs is less well understood. This study examined the temporal association between NPC changes and PTSD symptom changes in two distinct intensive PTSD treatment samples.

Methods

Data from 502 veterans who completed a 3-week CPT-based intensive PTSD treatment program was used to test the extent to which lagged NPC measurement predicted the next occurring PTSD severity measurement using linear mixed effects regression models. PTSD severity was assessed every other day during treatment. NPCs were assessed at three treatment timepoints. A second sample of 229 veterans who completed a 2-week CPT-based intensive PTSD treatment program was used to replicate these findings.

Results

Across both intensive PTSD treatment programs, NPCs generally increased from intake the end of the first treatment week, which was followed by gradual decreases in NPCs throughout the rest of both programs. Change in NPCs during both the 3-week (b = .21, p < .001, R2 = .38) and the 2-week programs (b = 0.20, p < .001, R2 = .24) were significant predictors of change in PTSD symptom severity. However, the reverse was true as well, with change in PTSD severity predicting latter change in NPCs during both the 3-week (b = 1.51, p < .001, R2 = .37) and 2-week (b = 1.37, p < .001, R2 = .33) programs, further raising questions about temporality of the association between NPCs and PTSD symptom severity during treatment.

Conclusions

The present study demonstrated that changes in NPCs may not temporally precede changes in PTSD symptom severity in PTSD treatment samples. Instead, we observed earlier PTSD symptom changes and a bidirectional association between the two constructs across both samples. Clinically, the study supports the continued focus on NPCs as an important treatment target as they are an important indicator of successful PTSD treatment, even if they may not be a direct mechanism of treatment-based changes in PTSD severity. Future research should attempt to identify alternative mechanisms of change in CPT.
An attempted “suicide pact” in Covid-19 era – psychiatric perspectives
Authors: Nardi Benedetta , Del Prete Luca , Amatori Giulia , Carpita Barbara , Carmassi Claudia , Pompili Maurizio , Dell’Osso Liliana
Published: November 2022

Background

A "suicide pact" is a joint and actively induced death of two individuals with the essential and unavoidable characteristic of a mutual consent. One of the partners (dominant in the relationship, commonly male) usually induces the action and in most cases, it is the one who actively carries it out. Undiagnosed psychopathological dimension or pathological subthreshold traits are found in those who enter into suicide agreements, the presence of cluster B personality traits such as narcissistic or borderline is of particular relevance in the dominant partner, while in the submissive one dependent personality traits are more frequent. As in the case of other similar health emergencies, COVID-19 pandemic seems to lead to greater suicidality, including the "suicide pacts" of couples whose motivation varies including firstly financial problems, strictly followed by fear of infection and not being able to return home from abroad.

Case presentation

We reported a case of a couple who entered a suicide agreement consequently to the economic difficulties caused by COVID-19 pandemic, hospitalized in our department. Both partners were assessed with Adult Autism Subthreshold Spectrum (AdAS Spectrum) and both crossed the threshold for clinically relevant autistic traits (M = 67; F = 49).

Conclusion

This case further confirms the link between COVID-19 pandemics and suicidality. The role of autism spectrum traits as a vulnerability factor towards the development of severe psychopathological consequences after traumatic events is also stressed.
Development and psychometric assessment of the sexual-reproductive health profile of women with type-1 diabetes mellitus
Authors: Azimi Nasrin , Ozgoli Giti , Ebadi Abbas , Majd Hamid Alavi , Rajab Assadollah , Kiani Zahra , Bazzazian Shahin , Mokhtaryan-Gilani Tahereh
Published: November 2022

Background

To improve the sexual-reproductive health (SRH) of women with type-1 diabetes mellitus (T1DM), plans should be formulated on the basis of the existing situation. The situation can be examined by a valid tool conforming to the specific domains of SRH in the target group. The present study seeks to develop and assess the psychometric properties of the SRH Profile of Women with T1DM.

Method

Based on the extracted concepts of SRH Profile of Women with T1DM in a previously conducted study, a tool was designed using the following steps: The selection of the conceptual model, explaining the objectives, designing the roadmap and development of the tool. In the psychometric assessment phase, the content, face and construct validity (convergent validity and principal component analysis) were assessed with the participation of 365 married women of reproductive age with T1DM. The reliability of the tool was determined by the internal consistency method (Cronbach’s alpha) and its stability using the test-retest method (Intraclass Correlation Coefficients).

Results

The SRH Profile of Women with T1DM was formed with 53 items in two sections. Twenty-six items were about safe motherhood and reproductive system; 27 items were about the three components of concerns about the reproductive system health and function, sexual health and function, and violence related to T1DM. The three components in the second section explained 49.44% of the total variance. Cronbach’s alpha was 0.872 and the total intra-cluster correlation coefficient was 0.946.

Conclusion

SRH Profile of Women with T1DM is a valid, reliable, and specific tool for assessing sexual-reproductive health in women with type-1 diabetes mellitus.
Surveillance of tobacco use among young adolescents: trends and predictors across three years in Sousse, Tunisia
Authors: Zammit Nawel , Maatoug Jihene , Ghammam Rim , Fredj Sihem Ben , Dhouib Wafa , Ayouni Imen , Maatouk Amani , Belgacem Waad Ben , Ouertani Mohamed , Ghannem Hassen
Published: November 2022

Background

In developed countries, there was an overall decrease in tobacco use over the last decades. In Tunisia, a national strategy to reduce tobacco use was set up since 2008. However, this strategy was rarely evaluated. The objective of the current study was to examine the trends in tobacco use among the middle schoolchildren of the governorate of Sousse (Tunisia) between 2014 and 2016 and to determine predictors of its experimentation.

Methods

Three cross-sectional studies were conducted in 2014, 2015 and 2016 school years among middle schoolchildren randomly selected from the governorate of Sousse-Tunisia. The required sample size for each study was 760 participants. Each year, the same procedure was used to recruit pupils from the same middle schools. The same pre-established and pre-tested questionnaire was self-administered anonymously to participants in their classrooms.

Results

Lifetime tobacco use rose from 11% in 2014 to 17.3% in 2016 (p = 0.001). Across the 3 years of survey, predictors of lifetime tobacco use were: The male sex (OR, 95% CI: 4.4 [3.2-6.1]), age above 13 (OR, 95% CI: 2.3 [1.7-3.1]), lifetime illicit substances use (OR, 95% CI: 3.9 [1.1- 13.8), lifetime inhalant products use (OR, 95% CI: 2.2 [1.2-4.3]), tobacco use among the father (OR, 95% CI: 2.2 [1.2-4.3]), tobacco use among siblings (OR, 95% CI: 1.7 [1.2-2.4]) and current anxiety symptoms (OR, 95% CI: 1.8 [1.4-2.4]).

Conclusion

Lifetime tobacco use is in expansion among the young adolescents of Sousse. The current national tobacco prevention program should be strengthened and expanded to cover other substances use issues with emphasis on secondhand smoking and mental health problems.
Breakage risk of different sacroiliac screws in unilateral sacral fractures a finite element analysis
Authors: Ma Yupeng , Zhao Yong , Zou Dexin , Dong Shengjie , Sun Xiujiang , Cheng Gong , Lian Wei , Zhao Yuchi , Sun Tao , Wang Dan , Zhang Shudong
Published: November 2022

Objective

To compare the breakage risk of lengthened sacroiliac screws and ordinary sacroiliac screws to treat unilateral vertical sacral fractures and provide a reference for clinical application.

Methods

A finite element model of Tile C pelvic ring injury (unilateral type Denis II fracture of the sacrum) was produced. The sacral fractures were fixed with a lengthened sacroiliac screw and ordinary sacroiliac screw in 6 types of models. The maximal von Mises stresses and stress distributions of the two kinds of screws when standing on both feet were measured and compared.

Results

The maximal von Mises stress of the lengthened screw was less than that of the ordinary screw. Compared with ordinary screw, the stress distribution in the lengthened screw was more homogeneous.

Conclusions

The breakage risk of screws fixed in double segments is lower than that of screws fixed in single segments, the breakage risk of lengthened screws is lower than that of ordinary screws, and the breakage risk of screws fixed in S2 segments is lower than that of screws fixed in S1 segments.
Biomechanical comparison of different prosthetic reconstructions in total en bloc spondylectomy: a finite element study
Authors: Xu Hanpeng , Wang Xiaodong , Han Ye , Jiang Yuanyuan , Wang Jianzhong , Zhang Xiong , Miao Jun
Published: November 2022

Objective

To analyse and compare the biomechanical differences between 3D-printed prostheses, titanium mesh cages and poorly matched titanium mesh cages in total en bloc spondylectomy (TES).

Methods

The finite element model of T10-L2 for healthy adults was modified to make three models after T12 total spondylectomy. These models were a 3D-printed prosthesis, titanium mesh cage and prosthesis-endplate mismatched titanium mesh cage for reconstruction. The range of motion (ROM), stress distribution of the endplate and internal fixation system of three models in flexion and extension, lateral bending and axial rotation were simulated and analysed by ABAQUS.

Result

In flexion, due to the support of the anterior prosthesis, the fixation system showed the maximum fixation strength. The fixation strength of the 3D-printed prosthesis model was 26.73 N·m /°, that of the TMC support model was 27.20 N·m /°, and that of the poorly matched TMC model was 24.16 N·m /°. In flexion, the L1 upper endplate stress of the poorly matched TMC model was 35.5% and 49.6% higher than that of the TMC and 3D-printed prosthesis, respectively. It was 17% and 28.1% higher in extension, 39.3% and 42.5% higher in lateral bending, and 82.9% and 91.2% higher in axial rotation, respectively. The lower endplate of T11 showed a similar trend, but the magnitude of the stress change was reduced. In the stress analysis of the 3D-printed prosthesis and TMC, it was found that the maximum stress was in flexion and axial rotation, followed by left and right bending, and the least stress was in extension. However, the mismatched TMC withstood the maximum von Mises stress of 418.7 MPa (almost twice as much as the buckling state) in rotation, 3 times and 5.83 times in extension, and 1.29 and 2.85 times in lateral bending, respectively.

Conclusion

Different prostheses with good endplate matching after total spondylectomy can obtain effective postoperative stable support, and the reduction in contact area caused by mismatch will affect the biomechanical properties and increase the probability of internal fixation failure.
Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease
Authors: Retnakaran Ravi , Shah Baiju R.
Published: November 2022

Background

Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses.

Methods

Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM−/CVD+); those with GDM but no CVD (GDM+/CVD−); and those with neither GDM nor CVD (GDM−/CVD−). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3±3.0 and 4.8±3.4 times over follow-up.

Results

On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM−/CVD− to GDM+/CVD− to GDM−/CVD+ to GDM+/CVD+ (all p<0.0001). At each point in time, each of the lipid and glycemic measures was significantly worse in GDM+/CVD+ compared to GDM+/CVD− (all p<0.001). Moreover, among women who did not develop CVD, all lipid and glycemic measures were significantly worse in those with previous GDM (all p<0.001 for GDM+/CVD− vs GDM−/CVD−). Mediation analyses revealed that the dominant determinants of CVD risk in women with GDM were A1c (56.0% mediation, 95%CI 47.4–67.8) and fasting glucose (47.4%, 38.8–60.8), followed by HDL (25.2%, 21.3–30.7) and triglycerides (12.1%, 9.7–15.6). Upon exclusion of those who developed diabetes during follow-up, the key determinants were HDL (40.8%), fasting glucose (37.7%), A1c (28.6%), triglycerides (21.0%), and LDL (9.9%).

Conclusions

Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population.
Identification of long non-coding RNA using single nucleotide epimutation analysis: a novel gene discovery approach
Authors: Kerachian Mohammad Amin , Azghandi Marjan
Published: November 2022

Background

Long non-coding RNAs (lncRNAs) are involved in a variety of mechanisms related to tumorigenesis by functioning as oncogenes or tumor-suppressors or even harboring oncogenic and tumor-suppressing effects; representing a new class of cancer biomarkers and therapeutic targets. It is predicted that more than 35,000 ncRNA especially lncRNA are positioned at the intergenic regions of the human genome. Emerging research indicates that one of the key pathways controlling lncRNA expression and tissue specificity is epigenetic regulation.

Methods

In the current article, a novel approach for lncRNA discovery based on the intergenic position of most lncRNAs and a single CpG site methylation level representing epigenetic characteristics has been suggested.

Results

Using this method, a novel antisense lncRNA named LINC02892 presenting three transcripts without the capacity of coding a protein was found exhibiting nuclear, cytoplasmic, and exosome distributions.

Conclusion

The current discovery strategy could be applied to identify novel non-coding RNAs influenced by methylation aberrations.
Examining the variations in the implementation of interventions to address stillbirth from the national to subnational levels: experiences from Uganda
Authors: Ssegujja Eric , Andipatin Michelle
Published: November 2022

Background

The current global burden of stillbirth disproportionately affects regions such as sub-Saharan Africa, where Uganda is located. To respond to this burden, policies made at the national level were diffused from the centre and translated into service delivery at the district level, which is charged with implementation under the decentralization of health services arrangement. Variations emerge whenever policy recommendations are moved from national to subnational levels, with some aspects often lost along the way. Tools are available to facilitate knowledge of determinants of policy and innovation implementation within the healthcare system. However, the extent to which these have been applied to explain variations in implementation of interventions to address stillbirth reduction in Uganda remains scant. The aim of this article was to examine the variations in the implementation of interventions to address stillbirth from the national to the subnational levels in Uganda using the Consolidated Framework for Implementation Research (CFIR).

Methods

The study adopted a qualitative case study design. Data were collected from a purposively selected sample of key informants drawn from both the national and subnational levels. All interviews were conducted in English and transcribed verbatim. ATLAS.ti was used to guide the coding process, which used a codebook developed following the CFIR domains as codes and constructs as sub-codes. Analysis followed a content analysis technique.

Results

National-level factors that favoured implementation of interventions to address stillbirth included the desire to comply with global norms, incentives to improve performance for stillbirth reduction indicators for better comparison with global peers, and clear policy alternatives as process implementation advanced by champions. Variations at the subnational level revealed aspirations to address service delivery gaps which fell within maternal health routine standard of care and ongoing health systems strengthening initiatives. Coalescing existing networks around maternal and child health was a key mobilization factor for advocacy and programming, with a promise that the set targets would be operationalized at the subnational level. The key champions were defined by their official roles within the district health systems, which enhanced accountability. Feedback and reflection were distinguished from the national to subnational through joint assemblies and formal audit reviews, respectively.

Conclusions

A heavy influence of the global events directed national-level adaptation of interventions to address stillbirth. Implementation context at the subnational level led to local adaptation and translation of policy provisions from the national level to suit the context, which to a greater extent explains the variations in the final content of policy provisions delivered.
The prevalence and management of chronic pain in the Chinese population: findings from the China Pain Health Index (2020)
Authors: Jiang Yingying , Xu Tingling , Mao Fan , Miao Yu , Liu Botao , Xu Liyuan , Li Lingni , Sternbach Nikoletta , Zhou Maigeng , Fan Bifa
Published: November 2022

Background

Chronic pain is a common disease; about 20% of people worldwide suffer from it. While compared with the research on the prevalence and management of chronic pain in developed countries, there is a relative lack of research in this field in China. This research aims to construct the China Pain Health Index (CPHI) to evaluate the current status of the prevalence and management of chronic pain in the Chinese population.

Methods

The dimensions and indicators of CPHI were determined through literature review, Delphi method, and analytical hierarchy process model, and the original values ​​of relevant indicators were obtained by collecting multi-source data. National and sub-provincial scores of CPHI (2020) were calculated by co-directional transformation, standardization, percentage transformation of the aggregate, and weighted summation.

Results

The highest CPHI score in 2020 is Beijing, and the lowest is Tibet. The top five provinces are Beijing (67.64 points), Shanghai (67.04 points), Zhejiang (65.74 points), Shandong (61.16 points), and Tianjin (59.99 points). The last five provinces are Tibet (33.10 points), Ningxia (37.24 points), Guizhou (39.85 points), Xinjiang (39.92 points), and Hainan (40.38 points). The prevalence of chronic pain is severe in Heilongjiang, Chongqing, Guizhou, Sichuan, and Fujian. Guizhou, Hainan, Xinjiang, Beijing, and Guangdong display a high burden of chronic pain. The five provinces of Guangdong, Shanghai, Beijing, Jiangsu, and Zhejiang have better treatment for chronic pain, while Tibet, Qinghai, Jilin, Ningxia, and Xinjiang have a lower quality of treatment. Beijing, Shanghai, Qinghai, Guangxi, and Hunan have relatively good development of chronic pain disciplines, while Tibet, Sichuan, Inner Mongolia, Hebei, and Guizhou are relatively poor.

Conclusion

The economically developed provinces in China have higher CPHI scores, while economically underdeveloped areas have lower scores. The current pain diagnosis and treatment situation in economically developed regions is relatively good, while that in financially underdeveloped areas is rather poor. According to the variations in the prevalence and management of chronic pain among populations in different provinces in China, it is necessary to implement chronic pain intervention measures adapted to local conditions.
Single cell profiling of CD45+ spinal cord cells reveals microglial and B cell heterogeneity and crosstalk following spinal cord injury
Authors: Fisher Elizabeth S. , Amarante Matthew A. , Lowry Natasha , Lotz Steven , Farjood Farhad , Temple Sally , Hill Caitlin E. , Kiehl Thomas R.
Published: November 2022

Background

Immune cells play crucial roles after spinal cord injury (SCI). However, incomplete knowledge of immune contributions to injury and repair hinders development of SCI therapies. We leveraged single-cell observations to describe key populations of immune cells present in the spinal cord and changes in their transcriptional profiles from uninjured to subacute and chronic stages of SCI.

Methods

Deep-read single-cell sequencing was performed on CD45+ cells from spinal cords of uninjured and injured Swiss-webster mice. After T9 thoracic contusion, cells were collected 3-, 7-, and 60-day post-injury (dpi). Subpopulations of CD45+ immune cells were identified informatically, and their transcriptional responses characterized with time. We compared gene expression in spinal cord microglia and B cell subpopulations with those in published models of disease and injury. Microglia were compared with Disease Associated Microglia (DAM) and Injury Responsive Microglia (IRM). B cells were compared to developmental lineage states and to an Amyotrophic Lateral Sclerosis (ALS) model.

Results

In uninjured and 7 dpi spinal cord, most CD45+ cells isolated were microglia while chronically B cells predominated. B cells accumulating in the spinal cord following injury included immature B to mature stages and were predominantly found in the injury zone. We defined diverse subtypes of microglia and B cells with altered gene expression with time after SCI. Spinal cord microglia gene expression indicates differences from brain microglia at rest and in inflammatory states. Expression analysis of signaling ligand–receptor partners identified microglia–B cell interactions at acute and chronic stages that may be involved in B cell recruitment, retention, and formation of ectopic lymphoid follicles.

Conclusions

Immune cell responses to SCI have region-specific aspects and evolve with time. Developmentally diverse populations of B cells accumulate in the spinal cord following injury. Microglia at subacute stages express B cell recruitment factors, while chronically, they express factors predicted to reduce B cell inflammatory state. In the injured spinal cord, B cells create ectopic lymphoid structures, and express secreted factors potentially acting on microglia. Our study predicts previously unidentified crosstalk between microglia and B cells post-injury at acute and chronic stages, revealing new potential targets of inflammatory responses for SCI repair warranting future functional analyses.
Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination
Authors: Hwang Mihyun , Savarin Carine , Kim Jihye , Powers Jennifer , Towne Natasha , Oh Hyunsuk , Bergmann Cornelia C.
Published: November 2022

Background

Triggering receptor expressed on myeloid cells 2 (Trem2) plays a protective role in neurodegenerative diseases. By contrast, Trem2 functions can exacerbate tissue damage during respiratory viral or liver infections. We, therefore, investigated the role of Trem2 in a viral encephalomyelitis model associated with prominent Th1 mediated antiviral immunity leading to demyelination.

Methods

Wild-type (WT) and Trem2 deficient (Trem2−/−) mice were infected with a sublethal glia tropic murine coronavirus (MHV–JHM) intracranially. Disease progression and survival were monitored daily. Leukocyte accumulation and pathological features including demyelination and axonal damage in spinal cords (SC) were determined by flow cytometry and tissue section immunofluorescence analysis. Expression of select inflammatory cytokines and chemokines was measured by RT-PCR and global myeloid cell gene expression in SC-derived microglia and infiltrated bone-marrow-derived macrophages (BMDM) were determined using the Nanostring nCounter platform.

Results

BMDM recruited to SCs in response to infection highly upregulatedTrem2mRNA compared to microglia coincident with viral control. Trem2 deficiency did not alter disease onset or severity, but impaired clinical recovery after onset of demyelination. Disease progression inTrem2−/−mice could not be attributed to altered virus control or an elevated proinflammatory response. A prominent difference was increased degenerated myelin not associated with the myeloid cell markers IBA1 and/or CD68. Gene expression profiles of SC-derived microglia and BMDM further revealed that Trem2 deficiency resulted in impaired upregulation of phagocytosis associated genesLplandCd36in microglia, but a more complex pattern in BMDM.

Conclusions

Trem2 deficiency during viral-induced demyelination dysregulates expression of other select genes regulating phagocytic pathways and lipid metabolism, with distinct effects on microglia and BMDM. The ultimate failure to remove damaged myelin is reminiscent of toxin or autoimmune cell-induced demyelination models and supports that Trem2 function is regulated by sensing tissue damage including a dysregulated lipid environment in very distinct inflammatory environments.
Fetuin-A alleviates neuroinflammation against traumatic brain injury-induced microglial necroptosis by regulating Nrf-2/HO-1 pathway
Authors: Zhao Pengzhan , Wei Yutian , Sun Guangchi , Xu Lei , Wang Tian , Tian Yufei , Chao Honglu , Tu Yiming , Ji Jing
Published: November 2022

Background

The microglia-mediated inflammatory response is a vital mechanism of secondary damage following traumatic brain injury (TBI), but the underlying mechanism of microglial activation is unclear.

Methods

Controlled cortical impact (CCI) was induced in adult male C57BL/6J mice, and glutamate was used to construct a classical in vitro injury model in the primary microglia. Microglial activation was determined by western blot and immunostaining. The inflammatory factors were measured by enzyme-linked immunosorbent assay. The oxidative stress marker and mitochondrial reactive oxygen species (ROS) were measured by immunoblotting and MitoSox Red staining. Transmission electron microscopy was used to observe the typical morphology of necroptotic cells.

Results

Our quantitative proteomics identified 2499 proteins; 157 were significantly differentially expressed in brain tissue between the 6 h after CCI (CCI6h) group and sham group, and 109 were significantly differentially expressed between the CCI24h and sham groups. Moreover, compared with the sham group, the terms “acute-phase response”, “inflammation”, and “protein binding” were significantly enriched in CCI groups. Fetuin-A, a liver-secreted acute-phase glycoprotein, was involved in these biological processes. Using an experimental TBI model, we found that the Fetuin-A level peaked at 6 h and then decreased gradually. Importantly, we showed that administration of Fetuin-A reduced the cortical lesion volume and edema area and inhibited the inflammatory response, which was associated with suppressing microglial necroptosis, thus decreasing microglial activation. Furthermore, administration of Fetuin-A attenuated mitochondrial oxidative stress in glutamate-treated microglial cells, which is a critical mechanism of necroptosis suppression. In addition, we demonstrated that Fetuin-A treatment promoted translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus in vivo; however, the Nrf-2 inhibitor ML385 and si-heme oxygenase-1 (si-HO-1) disrupted the regulation of oxidative stress by Fetuin-A and induced increased ROS levels and necroptosis in glutamate-treated microglial cells. Fetuin-A also protected neurons from adverse factors in vivo and in vitro.

Conclusions

Our results demonstrated that Fetuin-A activated Nrf-2/HO-1, suppressed oxidative stress and necroptosis levels, and thereby attenuates the abnormal inflammatory response following TBI. The findings suggest a potential therapeutic strategy for TBI treatment.
Loss of Brca1 and Trp53 in adult mouse mammary ductal epithelium results in development of hormone receptor-positive or hormone receptor-negative tumors, depending on inactivation of Rb family proteins
Authors: Szabova Ludmila , Gordon Melanie B. , Lu Lucy , Pate Nathan , Bassel Laura , Iacovelli Anthony J. , Karim Baktiar , Homan Philip J. , Householder Deborah B. , Guerin Theresa M. , Burkett Sandra , Day Amanda M. , Custer Wendi , Weaver Ohler Zoe
Published: November 2022

Background

Breast cancer is a heterogenous disease with several histological and molecular subtypes. Models that represent these subtypes are essential for translational research aimed at improving clinical strategy for targeted therapeutics.

Methods

Different combinations of genetic aberrations (Brca1 and Trp53 loss, and inhibition of proteins of the Rb family) were induced in the mammary gland by injection of adenovirus expressing Cre recombinase into the mammary ducts of adult genetically engineered mice. Mammary tumors with different genetic aberrations were classified into molecular subtypes based on expression of molecular markers and RNAseq analysis. In vitro potency assays and Western blots were used to examine their drug sensitivities.

Results

Induction of Brca1 and Trp53 loss in mammary ductal epithelium resulted in development of basal-like hormone receptor (HR)-negative mammary tumors. Inhibition of Rb and Trp53 loss or the combination of Rb, Trp53 and Brca1 aberrations resulted in development of luminal ductal carcinoma positive for ER, PR, and Her2 expression. HR positivity in tumors with Rb, Trp53 and Brca1 aberrations indicated that functionality of the Rb pathway rather than Brca1 status affected HR status in these models. Mammary tumor gene expression profiles recapitulated human basal-like or luminal B breast cancer signatures, but HR-positive luminal cancer models were endocrine resistant and exhibited upregulation of PI3K signaling and sensitivity to this pathway inhibition. Furthermore, both tumor subtypes were resistant to CDK4/6 inhibition.

Conclusions

Examination of molecular expression profiles and drug sensitivities of tumors indicate that these breast cancer models can be utilized as a translational platform for evaluation of targeted combinations to improve chemotherapeutic response in patients that no longer respond to hormone therapy or that are resistant to CDK4/6 inhibition.
Comparative analysis of the anthelmintic efficacy of European heather extracts on Teladorsagia circumcincta and Trichostrongylus colubriformis egg hatching and larval motility
Authors: Shepherd Francesca , Chylinski Caroline , Hutchings Michael R. , Lima Joana , Davidson Ross , Kelly Robert , Macrae Alastair , Salminen Juha-Pekka , Engström Marica T. , Maurer Veronika , Steinshamn Håvard , Fittje Susanne , Perez Angela Morell , García Rocío Rosa , Athanasiadou Spiridoula
Published: November 2022

Background

Gastrointestinal nematode (GIN) control is traditionally achieved with the use of anthelmintic drugs, however due to regulations in organic farming and the rise in anthelmintic resistance, alternatives are sought after. A promising alternative is the use of bioactive plant feeding due to the presence of plant secondary metabolites (PSMs) such as proanthocyanidins (PAs). This study focussed on the perennial shrub heather (Ericaceae family), a plant rich in PAs, highly abundant across Europe and with previously demonstrated anthelmintic potential.

Methods

In vitro assays were used to investigate heather’s anthelmintic efficacy against egg hatching and larval motility. Heather samples were collected from five European countries across two seasons, and extracts were tested against two GIN species: Teladorsagia circumcincta and Trichostrongylus colubriformis. Polyphenol group-specific ultraperformance liquid chromatography-tandem mass spectrometry analysis was performed to identify relevant polyphenol subgroups present, including the PA concentration and size and ratio of the subunits. Partial least squares analysis was performed to associate efficacy with variation in PSM composition.

Results

Heather extracts reduced egg hatching of both GIN species in a dose-dependent manner by up to 100%, while three extracts at the highest concentration (10 mg/ml) reduced larval motility to levels that were not significantly different from dead larvae controls. PAs, particularly the procyanidin type, and flavonol derivatives were associated with anthelmintic activity, and the particular subgroup of polyphenols associated with the efficacy was dependent on the GIN species and life stage.

Conclusions

Our results provide in vitro evidence that heather, a widely available plant often managed as a weed in grazing systems, has anthelmintic properties attributed to various groups of PSMs and could contribute to sustainable GIN control in ruminant production systems across Europe.

Graphical Abstract
Plasma adiponectin levels predict cognitive decline and cortical thinning in mild cognitive impairment with beta-amyloid pathology
Authors: Kim Keun You , Ha Junghee , Kim Minae , Cho So Yeon , Kim Hyunjeong , Kim Eosu ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2022

Background

Blood adiponectin and leptin are adipokines that emerged as potential biomarkers for predicting Alzheimer’s disease (AD) owing to their strong connection with obesity. Although obesity affects the relation between beta-amyloid (Aβ) aggregation and cognitive decline, the longitudinal interactive effect of adipokines and Aβ on cognition and brain structures in humans remains unexplored. Hence, we investigated whether plasma levels of adiponectin and leptin are associated with future cognitive decline and cortical thinning across Aβ conditions (Aβ [+] and Aβ [−]) in individuals with mild cognitive impairment (MCI).

Methods

Of 156 participants with MCI from the longitudinal cohort study of Alzheimer’s Disease Neuroimaging Initiative (ADNI), 31 were Aβ (−) and 125 were Aβ (+) as determined by CSF analysis. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores and the thickness of the parahippocampal and entorhinal cortices were used to evaluate cognition and brain structure, respectively. After stratifying groups by Aβ conditions, the association of cognitive and brain structural changes with baseline plasma levels of adiponectin and leptin was examined.

Results

Of the total 156 participants, 51 were women (32.7%). The mean age of participants was 74.5 (standard deviation 7.57), and the mean follow-up period was 54.3 months, without a difference between the Aβ (+) and (−) groups. After adjustment for confounders, higher plasma adiponectin levels were associated with a faster increase in ADAS-Cog scores, indicating faster cognitive decline under the Aβ (+) condition (beta = 0.224, p = 0.018). Likewise, participants with higher plasma adiponectin presented faster cortical thinning in the bilateral parahippocampal cortices under the Aβ (+) condition (beta = − 0.004, p = 0.012 for the right side; beta = − 0.004, p = 0.025 for the left side). Interestingly, plasma adiponectin levels were not associated with longitudinal ADAS-Cog scores or cortical thickness in the Aβ (−) condition. Plasma leptin levels were not predictive of cognition or cortical thickness regardless of Aβ status.

Conclusion

Plasma adiponectin can be a potential biomarker for predicting the speed of AD progression in individuals with Aβ (+) MCI.
Secret shopper studies: an unorthodox design that measures inequities in healthcare access
Authors: Rankin Kelsey A. , Mosier-Mills Alison , Hsiang Walter , Wiznia Daniel H.
Published: November 2022

Secret shopper studies are particularly potent study designs that allow for the gathering of objective data for a variety of research hypotheses, including but not limited to, healthcare delivery, equity of healthcare, and potential barriers to care. Of particular interest during the COVID-19 pandemic, secret shopper study designs allow for the gathering of data over the phone. However, there is a dearth of literature available on appropriate methodological practices for these types of studies. To make these study designs more widely accessible, here we outline the case for using the secret shopper methodology and detail best practices for designing and implementing them.
Stellate ganglion block relieves acute lung injury induced by severe acute pancreatitis via the miR-155-5p/SOCS5/JAK2/STAT3 axis
Authors: Wang Lei , Yuan Na , Li Yuanli , Ma Qinqin , Zhou Ying , Qiao Zhifei , Li Shutie , Liu Chunyan , Zhang Liqian , Yuan Meng , Sun Jianjing
Published: November 2022

Acute lung injury (ALI), a prevalent complication of severe acute pancreatitis (SAP), is also a leading contributor to respiratory failure and even death of SAP patients. Here, we intended to investigate the function and mechanism of stellate ganglion block (SGB) in ameliorating SAP-induced ALI (SAP-ALI). We engineered an SAP-ALI model in rats and treated them with SGB. HE staining and the dry and wet method were implemented to evaluate pathological alterations in the tissues and pulmonary edema. The rats serum changes of the profiles of TNF-α, IL-6, IL-1β, and IL-10 were examined. The profiles of miR-155-5p and SOCS5/JAK2/STAT3 were detected. Functional assays were performed for confirming the role of miR-155-5p in modulating the SOCS5/JAK2/STAT3 pathway in pulmonary epithelial cells. Our findings revealed that SGB vigorously alleviated SAP rat lung tissue damage and lung edema and lessened the generation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. SGB enhanced SOCS5 expression, hampered miR-155-5p, and suppressed JAK2/STAT3 pathway activation. As evidenced by mechanism studies, miR-155-5p targeted the 3′UTR of SOCS5 and repressed its expression, hence resulting in JAK2/STAT3 pathway activation. During animal trials, we discovered that SGB ameliorated SAP-ALI, boosted SOCS5 expression, and mitigated the levels of pro-inflammatory factors and miR-155-5p in the plasma. In vitro, miR-155-5p overexpression substantially facilitated pulmonary epithelial cell apoptosis, inflammation, and JAK2/STAT3 pathway activation and restrained SOCS5 expression. All in all, our work hinted that SGB could modulate the miR-155-5p/SOCS5/JAK2/STAT3 axis to alleviate SAP-ALI.
Changing mega-events’ spatial strategies and cultural policy: scaling down, spacing out, and assembling organizations in the cases of London and Milan
Authors: Jones Zachary M. , Di Vita Stefano , Ponzini Davide
Published: November 2022

Despite the proposed ‘certainty’ in a city or region hosting a mega-event, there has long been issues of uncertainty surrounding the planning and implementation of what have until now essentially been mega-projects. Large events have found a variety of ways to adapt and respond to unforeseen circumstances due to political conflicts, planning of oversize venues, limited time of implementation, and legacies that are difficult to manage. Considering the further increased uncertainty surrounding the planning of mega-events as a result of the COVID-19 pandemic, this paper examines how an accompanying cultural component—e.g., the Cultural Olympiad—may help cities that plan for events like the Olympics transition toward diversified drivers and long-term legacy. In particular, the case of cultural offering in Milan between the two mega-events of Expo 2015 and the upcoming 2026 Milano-Cortina Olympic Games shows how host cities can address growing uncertainty through the expanded role of a cultural programme combined with the rescaling of traditional mega-event formats. With this purpose, 2012 London Cultural Olympiad has been selected as an antecedent example—with positive and negative outcomes—to critically review the relationships between the Olympics and the Cultural Olympiad, as well as their widespread spatial strategy and public engagement. In addition, the paper offers more general conclusions regarding learning potentials of jointly studying mega-events and cultural policy.
The German S3 guideline on titanium hypersensitivity in implant dentistry: consensus statements and recommendations
Authors: Müller-Heupt Lena Katharina , Schiegnitz Eik , Kaya Sebahat , Jacobi-Gresser Elisabeth , Kämmerer Peer Wolfgang , Al-Nawas Bilal
Published: November 2022

Background

There is currently a lack of guidelines for clinicians regarding titanium hypersensitivity in implant dentistry. Diagnostic tests such as the epicutaneous test or the lymphocyte transformation test showed inconsistent results regarding reliability and validity and thus, evidence-based consensus recommendations regarding diagnostic and therapeutic options may be helpful in clinical decision-making. Therefore, the German S3 guideline on titanium hypersensitivity in implant dentistry was developed.

Findings

In the objectives, procedure, voting method and venue were defined and the consensus participants were invited. A systematic literature research was performed, and the overall quality of the evidence was rated according to the GRADE working group. Eight recommendations were formulated within the framework of a structured consensus conference under independent moderation and could be voted on with strong consensus (> 95% agreement). The formulated statements and recommendations were developed in small groups according to the guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) and were discussed and agreed upon in the plenum.

Conclusions

For reasonable decision-making, a patient’s clinical symptoms should be regarded as leading parameters, which are usually expressed by a local inflammatory reaction with subsequent disturbed osseous integration. Allergy tests, such as the epicutaneous test or the lymphocyte transformation test are not helpful in titanium intolerance assessments, since these tests indicate T cell-mediated allergies, which are not observed in titanium intolerance reactions. Other metals and impurities that might be present in superstructures or alloys also need to be considered as the cause of an intolerance reaction and a trigger for contact sensitization. In the case of a suspected titanium particle-related, local immunologically induced inflammatory reaction with subsequent impaired osseous integration, dental ceramic implants can be considered as a therapeutic option.

Graphical Abstract
Remote working in public involvement: findings from a mixed methods study
Authors: Jones Elisa , Frith Lucy , Gabbay Mark , Tahir Naheed , Hossain Muhammad , Goodall Mark , Bristow Katie , Hassan Shaima
Published: November 2022

Background

This paper considers remote working in patient public involvement and engagement (PPIE) in health and social care research. With the advent of the Covid-19 pandemic and associated lock-down measures in the UK (from March 2020), PPIE activities switched to using remote methods (e.g., online meetings), to undertake involvement. Our study sought to understand the barriers to and facilitators for remote working in PPIE by exploring public contributors’ and PPIE professionals’ (people employed by organisations to facilitate and organise PPIE), experiences of working remotely, using online and digital technologies. A particular focus of our project was to consider how the ‘digital divide’ might negatively impact on diversity and inclusion in PPIE in health and social care research.

Methods

We used a mixed method approach: online surveys with public contributors involved in health and social care research, online surveys with public involvement professionals, and qualitative interviews with public contributors. We co-produced the study with public contributors from its inception, design, subsequent data analysis and writing outputs, to embed public involvement throughout the study.

Results

We had 244 respondents to the public contributor survey and 65 for the public involvement professionals (PIPs) survey and conducted 22 qualitative interviews. Our results suggest public contributors adapted well to working remotely and they were very positive about the experience. For many, their PPIE activities increased in amount and variety, and they had learnt new skills. There were both benefits and drawbacks to working remotely. Due to ongoing Covid restrictions during the research project, we were unable to include people who did not have access to digital tools and our findings have to be interpreted in this light.

Conclusion

Participants generally favoured a mixture of face-to-face and remote working. We suggest the following good practice recommendations for remote working in PPIE: the importance of a good moderator and/or chair to ensure everyone can participate fully; account for individual needs of public contributors when planning meetings; provide a small expenses payment alongside public contributor fees to cover phone/electricity or WiFi charges; and continue the individual support that was often offered to public contributors during the pandemic.