bluuebunny/crossref_metadata_2025 huggingface dataset:
Double Jeopardy: Prematurity and Congenital Heart Disease—What's Known and Why It's Important
Authors: Costello John M. , Kim Faith , Polin Richard , Krishnamurthy Ganga
Published: December 2021

This article is based on a composite of talks presented during the Double Jeopardy: Prematurity and Congenital Heart Disease Plenary Session at NeoHeart 2020, a global virtual conference.

Prematurity and low weight remain significant risk factors for mortality after neonatal cardiac surgery despite a steady increase in survival. Newer and lower weight thresholds for operability are constantly generated as surgeons gather proficiency, technical mastery, and experience in performing complex procedures on extremely small infants. The relationship between birth weight and survival after cardiac surgery is nonlinear with 2 kilograms (kg) being an inflection point below which marked decline in survival occurs.

The prevalence of congenital heart disease (CHD) in premature infants is more than twice that in term born infants. Increased risk of preterm birth in infants with CHD is most commonly due to spontaneous preterm birth and remains poorly understood.

Advances in Neonatal-Perinatal medicine have led to a marked improvement in survival of neonates born prematurely over the last several decades. However, the risk of severe morbidities including retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia and necrotizing enterocolitis remains significant in extremely low birth weight infants. Premature infants with CHD are at a greater risk of prematurity related morbidities than premature infants without CHD. Interventions that have been successful in decreasing the risk of these morbidities are addressed.
Linking Mentoring and Job Search Behavior: A Moderated Mediation Model
Authors: Lian Ruirui , Cai Wenjing , Chen Kun , Shen Hongru , Gao Xiaopei , Xu Binfeng , Jiang Lin
Published: December 2021

The present research aims to explore the impact of mentoring relationship on college graduates’ job search behavior among Chinese undergraduate students by examining the mediator of job search intention and the moderator of job search self-efficacy. A two-wave survey study was conducted in China ( N = 594). Our findings show a positive indirect relation between mentoring and college graduates’ job search behaviors through job search intention. The graduates’ job search self-efficacy positively moderated the indirect relationship such that when job search self-efficacy was higher, the influence of mentoring on behavior via job search intention was stronger. These findings extend the literature by clarifying how and when mentoring facilitates graduates’ job search behaviors and provide practical implications for facilitating a smooth school-to-work transition in China. As the first study that empirically clarifies why (through job search intention) and when (job search self-efficacy) mentoring function is positively related to job search behavior among Chinese undergraduate students, the present study contributes to the existing mentoring and job search literature. Future research is encouraged to extend the findings by integrating theory of planned behavior (TPB) with self-regulation theory toward deepening current understanding of how and when mentoring can contribute to a student’s success in job search behavior.
How Robust Is the p Factor? Using Multitrait-Multimethod Modeling to Inform the Meaning of General Factors of Youth Psychopathology
Authors: Watts Ashley L. , Makol Bridget A. , Palumbo Isabella M. , De Los Reyes Andres , Olino Thomas M. , Latzman Robert D. , DeYoung Colin G. , Wood Phillip K. , Sher Kenneth J.
Published: December 2021

We used multitrait-multimethod (MTMM) modeling to examine general factors of psychopathology in three samples of youths ( Ns = 2,119, 303, and 592) for whom three informants reported on the youth’s psychopathology (e.g., child, parent, teacher). Empirical support for the p-factor diminished in multi-informant models compared with mono-informant models: The correlation between externalizing and internalizing factors decreased, and the general factor in bifactor models essentially reflected externalizing. Widely used MTMM-informed approaches for modeling multi-informant data cannot distinguish between competing interpretations of the patterns of effects we observed, including that the p factor reflects, in part, evaluative consistency bias or that psychopathology manifests differently across contexts (e.g., home vs. school). Ultimately, support for the p factor may be stronger in mono-informant designs, although it does not entirely vanish in multi-informant models. Instead, the general factor of psychopathology in any given mono-informant model likely reflects a complex mix of variances, some substantive and some methodological.
Comparison of Cervical Sagittal Parameters Between Radiographs and Magnetic Resonance Images in Patients With Cervical Spondylotic Myelopathy
Authors: Xu Chongqing , Shen Qixing , Xu Jinhai , Ma Junming , Ye Jie , Mo Wen
Published: December 2021

Study Design

Observational study

Objective

As an important consideration of surgery, cervical sagittal balance is believed to be better assessed using standing radiograph than supine magnetic resonance imaging (MRI). However, few studies have researched this. Our study aimed to observe the correlations and differences in cervical sagittal parameters between radiograph and MRI in patients with cervical spondylotic myelopathy (CSM), and evaluate whether the change of position affects them.

Methods

We analyzed 84 patients, measuring Cobb angle (CA), T1 slope (T1S), neck tilt (NT), and thoracic inlet angle (TIA). Inter- and intra-parameter analyses were performed to identify any difference between standing radiograph and supine MRI. Statistical correlations and differences between the parameters were compared.

Results

There were excellent inter-observer agreement for each parameter (interclass correlation coefficient >.75), and significant differences were observed in each parameter between radiograph and magnetic resonance imaging ( P < .05). Strong correlations were noted between the same parameters in radiograph and MRI. Cobb angle, T1S, and neck tilt were significantly correlated with thoracic inlet angle on both radiograph and MRI, and CA was significantly correlated with T1S on both radiograph and MRI ( r: −1.0 to −.5 or .5 to 1.0).

Conclusion

Supine MRI obviously underestimated the value of CA, T1S, and TIA. Therefore, standing cervical radiographs should be obtained in CSM patients to assess and determine surgical strategy, not only supine MRI. Moreover, we observed that NT and TIA were not constant morphological parameters.
Phalloplasty With a Free Scapular Flap Improves Postoperative Sensation in Penile Reconstruction
Authors: Wu Qi , Yang Zhe , Ma Ning , Wang Weixin , Li Yangqun
Published: December 2021

Objective We aimed to evaluate both the long-term surgical outcomes and patient-reported outcomes of free scapular flap (FSF) phalloplasty. Method The same surgical team performed phalloplasty in 66 patients using a FSF between March 2000 and September 2018. All patients had at least 24 months of follow-up. The surgical techniques used, complications observed, and surgical and patient-reported outcomes were retrospectively described. Results A total of 66 patients with indications of penile trauma (n = 19), micropenis (n = 42), and self-amputation (n = 5) underwent FSF phalloplasty. Two patients (3%) had total flap necrosis and 1 (1.5%) had partial flap necrosis. The urethral complication rate was 18.2% (12/66 patients). All patients were able to void while standing after revision procedures or urethroplasty. We found that an FSF is a reliable donor site for penile reconstruction. Conclusion The FSF phalloplasty creates an esthetically pleasing penis and allows voiding while standing. Most patients can engage in sexual activity. The main drawbacks of using this method are that patients experience different degrees of sensory recovery, and patients undergoing surgery with the “tube-in-tube” technique may find they are be limited by the thickness of the flap. However, by making full use of residual tissue, such as the micropenis glans or scrotal skin, patients can obtain good tactile and erogenous sensation. We believe that using an FSF complements the existing phalloplasty techniques.
Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study
Authors: Wellings Elizabeth P. , Huang Tony Chieh-Ting , Li Jialun , Peterson Timothy E. , Hooke Alexander W. , Rosenbaum Andrew , Zhao Chunfeng D. , Behfar Atta , Moran Steven L. , Houdek Matthew T.
Published: December 2021

Background:

Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury.

Purpose:

To determine if a tendon’s intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold.

Study Design:

Controlled laboratory study.

Methods:

An in vivo rabbit Achilles tendon model was used and consisted of 3 groups: (1) Achilles tenotomy with suture repair, (2) Achilles tenotomy with suture repair and collagen scaffold, and (3) Achilles tenotomy with suture repair and collagen scaffold loaded with PEP at 1 × 1012 exosomes/mL. Each group consisted of 15 rabbits for a total of 45 specimens. Mechanical and histologic analyses were performed at both 3 and 6 weeks.

Results:

The load to failure and ultimate tensile stress were found to be similar across all groups ( P ≥ .15). The tendon cross-sectional area was significantly smaller for tendons treated with PEP compared with the control groups at 6 weeks, which was primarily related to an absence of external adhesions ( P = .04). Histologic analysis confirmed these findings, demonstrating significantly lower adhesion grade both macroscopically ( P = .0006) and microscopically ( P = .0062) when tendons were treated with PEP. Immunohistochemical staining showed a greater intensity for type 1 collagen for PEP-treated tendons compared with collagen-only or control tendons.

Conclusion:

Mechanical and histologic results suggested that healing in the PEP-treated group favored intrinsic healing (absence of adhesions) while control animals and animals treated with collagen only healed primarily via extrinsic scar formation. Despite a smaller cross-sectional area, treated tendons had the same ultimate tensile stress. This pilot investigation shows promise for PEP as a means of effectively treating tendon injuries and enhancing intrinsic healing.

Clinical Relevance:

The production of a cell-free, off-the-shelf product that can promote tendon regeneration would provide a viable solution for physicians and patients to enhance tendon healing and decrease adhesions as well as shorten the time required to return to work or sports.
Assessment of Resident Knowledge in Pediatric Rheumatology
Authors: Guglielmo-Roxby Tiffany , Louissaint Valerie , Ettinger Abigail , Llanos Adana , Cahill Ellen , Chefitz Dalya , Boneparth Alexis , Amato Indira , Moorthy Lakshmi Nandini
Published: December 2021

Pediatric Rheumatic illnesses are complex, chronic, and often multi-systemic. Our goal was to assess the efficacy of 2 standardized pediatric rheumatology lectures, administered to pediatric residents, in improving the pediatric residents’ knowledge and confidence in pediatric rheumatology. Two lectures, 1 hour each, were delivered by 2 residents and given 1 week apart to 28 pediatric residents. Pre- and post-tests assessed knowledge and residents’ self-rated competence. Change in knowledge was assessed using paired t-tests. Twenty-eight residents participated in the study. Sixty-three percent (17/27) had an improvement in score from pre-test to post-test. Thirty-seven percent (10/27) reported increased competence from pre-test to post-test. Ninety-six percent (22/23) of the residents found the lectures to be beneficial. Residents in the third post-graduate year (PGY3) cohort had the most significant improvement in scores. The lectures given to the pediatric residents increased pediatric knowledge and the pediatric residents found these lectures to be beneficial.
Program evaluation: improving the quality of life of older people in an urban slum in Bangladesh
Authors: Chowdhury Mostofa Kamal , Ahmad Nezamuddin , Biswas Fazle Noor , Farheen Nadia , Ferdous Lailatul , Akter Kazi Maksoda , Connor Stephen R.
Published: December 2021

Aims:

The study aimed to explore the quality and impact of care provided through an innovative palliative care project to improve the quality of life of older people in an urban informal settlement in Bangladesh.

Methods:

Center for Palliative Care (CPC) at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, in collaboration with the Worldwide Hospice Palliative Care Alliance (WHPCA) has been operating this community project since 2015. A cross-sectional observational design was used in this program evaluation study. A total of 594 people received services including 227 patients (Group-1) receiving regular and intensive palliative care and 367 patients with less intense needs (Group-2) receiving relatively less support based on need. In addition, current group-1 patients (total 114) and a matched cohort of 58 group-2 patients were interviewed with an experience of care survey questionnaire. Baseline and demographic data were presented in tables. The Z-test was used to measure mean statistical differences between two groups.

Results:

Multiple comorbidities were common. Pain was the most frequently noted physical symptom along with anxiety, sadness, and depression as common psychological concerns. Compassionate palliative care for the older people had significant ( p < 0.05) impact on psycho-social and spiritual care, caregiver training, responding to emergencies, and reduction of out of pocket healthcare expenditure among the intensive intervention group.

Conclusion:

Using a community-based approach following this model may play a significant part in expansion of palliative care throughout Bangladesh to meet the huge need and scarcity of such services.
Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy
Authors: Holland Elizabeth M. , Yates Bonnie , Ling Alex , Yuan Constance M. , Wang Hao-Wei , Stetler-Stevenson Maryalice , LaLoggia Michael , Molina John C. , Lichtenstein Daniel A. , Lee Daniel W. , Ligon John A. , Shalabi Haneen , Ahlman Mark A. , Shah Nirali N.
Published: December 2021

Chimeric antigen receptor (CAR) T cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non-CNS extramedullary disease (EMD) has not been well characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD. We conducted a retrospective review of B-ALL patients with non-CNS EMD who were screened for/enrolled on one of three CAR trials (CD19, CD22, and CD19/22) at our institution. Non-CNS EMD was identified according to histology or radiographic imaging at extramedullary sites excluding the cerebrospinal fluid and CNS parenchyma. Of ∼180 patients with relapsed/refractory B-ALL screened across multiple early-phase trials over an 8-year period, 38 (21.1%) presented with isolated non-CNS EMD (n = 5) or combined medullary/non-CNS EMD (n = 33) on 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging. A subset receiving CAR T cells (18 infusions) obtained FDG PET/CT scans preinfusion and postinfusion to monitor response. At best response, 72.2% (13 of 18) of patients showed a medullary minimal residual disease–negative complete remission and complete (n = 7) or partial (n = 6) non-CNS EMD response. Non-CNS EMD responses to CAR T cells were delayed (n = 3), and residual non-CNS EMD was substantial; rarely, discrepant outcomes (marrow response without EMD response) were observed (n = 2). Unique CAR-associated toxicities at non-CNS EMD sites were seen in select patients. CAR T cells are active in B-ALL non-CNS EMD. Still, non-CNS EMD response to CAR T cells may be delayed and suboptimal, particularly with multifocal disease. Serial FDG PET/CT scans are necessary for identifying and monitoring non-CNS EMD.
Nitro-fatty acids decrease type I interferons and monocyte chemoattractant protein 1 in ex vivo models of inflammatory arthritis
Authors: Hansen A. L. , Rahbek L. S. J. , Sørensen A. S. , Hundahl M. P. , Lomholt S. , Holm C. K. , Kragstrup Tue W.
Published: December 2021

Background

Inflammatory arthritis including rheumatoid arthritis (RA) and spondyloarthritis (SpA) is characterized by inflammation and destruction of the joints. Approximately one third of patients do not respond to first-line treatments. Nitro-fatty acids are bioactive lipids with anti-inflammatory properties and tissue-protective functions. The nitro-fatty acid 10-NO2-oleic acid (10-NO2-OA) is being tested in clinical trials for patients with fibrotic and inflammatory conditions. Here, we tested whether 10-NO2-OA could inhibit immune reactions involved in the inflammatory and joint destructive processes in inflammatory arthritis.

Methods

Synovial fluid and blood samples were obtained from 14 patients with active RA or SpA. The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) cultured for 48 h, SFMCs cultured for 21 days, and fibroblast-like synovial cells (FLSs) co-cultured with peripheral blood mononuclear cells (PBMCs) for 48 h. Cells were treated with or without 10-NO2-OA or the tumor necrosis factor alpha (TNFα) inhibitor etanercept. Supernatants were analyzed for type I interferon, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase 3 (MMP3) and tartrate resistant acid phosphatase (TRAP).

Results

In SFMCs cultured for 48 h, 10-NO2-OA dose-dependently decreased the secretion of bioactive type I interferons and MCP-1 but not MMP3 (P = 0.032, P = 0.0001, and P = 0.58, respectively). Both MCP-1 and MMP3 were decreased by etanercept (P = 0.0031 and P = 0.026, respectively). In SFMCs cultured for 21 days, 10-NO2-OA significantly decreased the production of MCP-1 but not TRAP (P = 0.027 and P = 0.1523, respectively). Etanercept decreased the production of TRAP but not MCP-1 (P < 0.001 and P = 0.84, respectively). In co-cultures of FLSs and PBMCs, 10-NO2-OA decreased the production of MCP-1 (P < 0.0001). This decrease in MCP-1 production was not seen with etanercept treatment (P = 0.47).

Conclusion

10-NO2-OA decreased the release of MCP-1 in three models of inflammatory arthritis. Of particular interest, 10-NO2-OA inhibited type I interferon, and 10-NO2-OA was more effective in reducing MCP-1 production in cultures dominated by FLSs compared with etanercept. Our results encourage clinical investigations of 10-NO2-OA in patients with inflammatory arthritis.
Relationship between internet research data of oral neoplasms and public health programs in the European Union
Authors: Lan Romain , Campana Fabrice , Tardivo Delphine , Catherine Jean-Hugues , Vergnes Jean-Noel , Hadj-Saïd Mehdi
Published: December 2021

Background

Tobacco and alcohol are the main risk factors for oral squamous cell carcinoma, the low survival rate of which is a public health problem. European-wide health policies (a prevention campaign, tobacco packaging) have been put in place to inform the population of the risks associated with consumption. Due to the increase in smoking among women, the incidence of this disease remains high. The identification of internet research data on the population could help to measure the impact of and better position these preventive measures. The objective was to analyze a potential temporal association between public health programs and interest in oral cancers on the internet in the European Union (EU).

Methods

A search of data from Google ©, Wikipedia © and Twitter © users in 28 European countries relating to oral cancer between 2004 and 2019 was completed. Bibliometric analysis of press and scientific articles over the same period was also performed. The association between these data and the introduction of public health programs in Europe was studied.

Results

There was a temporal association between changes in tobacco packaging and a significant increase in internet searches for oral cancer in seven countries. Unlike national policies and ad campaigns, the European awareness program Make Sense has had no influence on internet research. There was an asymmetric correlation in internet searches between publications on oral cancer from scientific articles or "traditional" media (weak association) and those from internet media such as Twitter © or Wikipedia © (strong association).

Conclusion

Our work highlights seven areas around which oral cancer awareness in Europe could be refocused, such as a change in the communication of health warnings on cigarette packs, the establishment of a more explicit campaign name regarding oral cancer, the involvement of public figures and associations in initiatives to be organized at the local level and the strengthening of awareness of the dangers of tobacco in the development of oral cancer.
Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity
Authors: Prado Carolina , Osorio-Barrios Francisco , Falcón Paulina , Espinoza Alexandra , Saez Juan José , Yuseff María Isabel , Pacheco Rodrigo
Published: December 2021

Background

Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+T cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here, we addressed the role of the dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in B cells in animal models of MS.

Methods

Mice harbouringDrd3-deficient orDrd3-sufficient B cells were generated by bone marrow transplantation into recipient mice devoid of B cells. In these mice, we compared the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC-function of B cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B cells display a fundamental APC-function in the CNS. APC-function was assessed in vitro by pulsing B cells with huMOG-coated beads and then co-culturing with MOG-specific T cells.

Results

Our data show that the selectiveDrd3deficiency in B cells abolishes the disease development in the huMOG-induced EAE model. Mechanistic analysis indicates that although DRD3-signalling did not affect the APC-function of B cells, DRD3 favours the CNS-tropism in a subset of pro-inflammatory B cells in the huMOG-induced EAE model, an effect that was associated with higher CXCR3 expression. Conversely, the results show that the selectiveDrd3 deficiencyin B cells exacerbates the disease severity in the pMOG-induced EAE model. Further analysis shows that DRD3-stimulation increased the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in the pMOG-induced EAE model.

Conclusions

Our findings demonstrate that DRD3 in B cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B cells with APC-function and promoting CNS-homing of B cells with anti-inflammatory features. Thus, these results show DRD3-signalling in B cells as a critical regulator of CNS-autoimmunity.
Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway
Authors: Wang Jun-ying , Zhang Yue , Chen Yu , Wang Yu , Li Shao-yuan , Wang Yi-fei , Zhang Zi-xuan , Zhang Jinling , Rong Peijing
Published: December 2021

Background

Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA).

Methods

There were control, model, taVNS, α7nAChR(−/−) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected.

Results

Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(−/−) rats and Hi MLA rats.

Conclusion

The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.
NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice
Authors: Sun Dan , Gao Guofang , Zhong Bihua , Zhang Han , Ding Shixin , Sun Zhenghao , Zhang Yaodong , Li Weizu
Published: December 2021

Background

Brain aging is an important risk factor in many human diseases, such as Alzheimer’s disease (AD). The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. However, it is still unclear when and how the neuroinflammation appears in the brain during aging process.

Methods

In this study, we observed the alterations of learning and memory impairments, neuronal damage, NLRP1 inflammasome activation, ROS production and NOX2 expression in the young 6-month-old (6 M) mice, presenile 16 M mice, and older 20 M and 24 M mice.

Results

The results indicated that, compared to 6 M mice, the locomotor activity, learning and memory abilities were slightly decreased in 16 M mice, and were significantly decreased in 20 M and 24 M mice, especially in the 24 M mice. The pathological results also showed that there were no significant neuronal damages in 6 M and 16 M mice, while there were obvious neuronal damages in 20 M and 24 M mice, especially in the 24 M group. Consistent with the behavioral and histological changes in the older mice, the activity of β-galactosidase (β-gal), the levels of ROS and IL-1β, and the expressions of NLRP1, ASC, caspase-1, NOX2, p47phox and p22phox were significantly increased in the cortex and hippocampus in the older 20 M and 24 M mice.

Conclusion

Our study suggested that NLRP1 inflammasome activation may be closely involved in aging-related neuronal damage and may be an important target for preventing brain aging.
Polytraumatization in young male refugees from the Middle East and its association with internalizing and externalizing symptoms
Authors: EL-Awad Usama , Reinelt Tilman , Braig Johanna , Nilles Hannah , Kerkhoff Denise , Schmees Pia , Rueth Jana-Elisa , Fathi Atefeh , Vasileva Mira , Petermann Franz , Eschenbeck Heike , Lohaus Arnold
Published: December 2021

Background

Young Middle Eastern male refugees are currently among the most vulnerable groups in Europe. Most of them have experienced potentially traumatic events (PTEs) such as rape, torture, or violent assaults. Compared to their peers, young refugees suffer more from internalizing and externalizing symptoms, especially when unaccompanied. Little is known about the cumulative impact of experiencing different types of PTEs on mental health outcomes (polytraumatization) of young male refugees from the Middle East. We investigated (1) whether there is a dose–response relationship between multiple PTE types experienced and mental health outcomes, (2) whether individual types of PTEs are particularly important, and (3) to what extent these are differentially associated with mental health outcomes among unaccompanied or accompanied peers.

Methods

In total, 151 young Middle Eastern male refugees in Germany (Mage = 16.81 years, SDage = 2.01) answered questionnaires on PTEs, mental health, and post-migration stress.

Results

Hierarchical regression analyses revealed, while controlling for age, duration of stay, unaccompanied status, and post-migration stress, (1) a dose–effect between PTE types on both internalizing and externalizing symptoms. Moreover, (2) regarding internalizing symptoms, violent family separation and experiencing life-threatening medical problems were particularly crucial. The latter was driven by unaccompanied refugees, who also reported higher levels of substance use.

Conclusions

The results extend findings from the literature and suggest that not only may greater polytraumatization be related to greater depression among refugees, but also to a range of other mental health outcomes from the internalizing and externalizing symptom domains. Furthermore, the results highlight the mental health risks that unaccompanied and accompanied refugee adolescents face after exposure to PTEs, and provide information for practitioners as well as researchers about event types that may be particularly relevant.
An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors
Authors: Nwanaji-Enwerem Jamaji C. , Chung Felicia Fei-Lei , Van der Laan Lars , Novoloaca Alexei , Cuenin Cyrille , Johansson Harriet , Bonanni Bernardo , Hubbard Alan E. , Smith Martyn T. , Hartman Sheri J. , Cardenas Andres , Sears Dorothy D. , Herceg Zdenko
Published: December 2021

Metformin and weight loss relationships with epigenetic age measures—biological aging biomarkers—remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20–0.86; P < 0.005). However, no significant epigenetic aging associations were observed by intervention arms. Consistent with published reports in non-cancer patients, 6 months of metformin therapy may be inadequate to observe expected epigenetic age deceleration. Longer duration studies are needed to better characterize these relationships.

Trial Registration: Registry Name: ClincialTrials.Gov.

Registration Number: NCT01302379.

Date of Registration: February 2011.

URL:https://clinicaltrials.gov/ct2/show/NCT01302379
Subcapsular hepatic hematoma as a complication of severe preeclampsia: a case report
Authors: Luhning Kiel , MacCormick Hilary , Macaulay Bruce , Saunders Marianna , Craig Catherine
Published: December 2021

Background

Subcapsular hepatic hematoma is a rare and life-threatening complication of pregnancy. It is most commonly associated with severe preeclampsia and hemolytic anemia, elevated liver enzymes, and low platelets syndrome. Patients with subcapsular hepatic hematoma typically present with epigastric, right upper quadrant or shoulder pain, nausea and vomiting, and/or shortness of breath. Here we describe a patient with a classic pain presentation, a large unruptured hematoma, and an unusual postpartum course.

Case

A 40-year-old gravida 1 para 0 Caucasian woman presented at 39 + 6 weeks gestational age with a 3-day history of new onset pain in an otherwise uncomplicated pregnancy. She described the pain along her right torso as severe, shooting, and sharp, but at times pleuritic in nature. She was found to have new onset preeclampsia and hemolytic anemia, elevated liver enzymes, and low platelets syndrome. Induction of labor was initiated and eventually she delivered by cesarean section. Her pain persisted in the postpartum period and abdominal computed tomography scan revealed a 16 cm subcapsular hepatic hematoma. Despite the hematoma being thin walled, conservative management was recommended by the general surgeon. She then re-presented on postpartum day 15 with tachypnea, dyspnea, and pleuritic chest pain. Secondary to the subcapsular hepatic hematoma, she then developed an infected and loculated, large pleural effusion. This required video-assisted thoracoscopic surgery before her eventual discharge home on postpartum day 21.

Conclusions

There should be high clinical suspicion of subcapsular hepatic hematoma in patients with persistent pain in the right upper quadrant of the abdomen. Urgent imaging to investigate for subcapsular hepatic hematoma is then indicated. Cesarean delivery without labor and treatment for severe preeclampsia should be undertaken if subcapsular hepatic hematoma is found. Conservative management and serial imaging are reasonable for the follow-up of a large, unruptured hematoma. Hepatic artery embolization should also be considered. Subcapsular hepatic hematoma may be complicated by infected pleural effusions and require video-assisted thoracoscopic surgery.
Response of soil biological properties and bacterial diversity to different levels of nitrogen application in sugarcane fields
Authors: Yang Shangdong , Xiao Jian , Liang Tian , He Weizhong , Tan Hongwei
Published: December 2021

To select an eco-friendly nitrogen (N) application level for sugarcane production, soil fertility and soil bacterial diversity under different nitrogen application levels were analyzed. Four levels of urea applications were high Nitrogen (H, 964 kg ha−1), medium Nitrogen (M, 482 kg ha−1), low Nitrogen (L, 96 kg ha−1) and no Nitrogen (CK, 0 kg ha−1) treatments, respectively. The results showed that the soil microbial biomass carbon and phosphorus were altered significantly by CK and L treatments. Moreover, the indexes of soil bacterial richness and diversity in the sugarcane field could be significantly improved by L. At the genus level, SC-I-84, Mycobacterium, Micropepsaceae, Saccharimonadales, Subgroup_2 and Acetobacteraceae were the unique dominant bacteria in the soil with the H treatment. JG30-KF-CM45 and Jatrophihabitans were the unique dominant genera in the M treatment. Subgroup_6, HSB_OF53-F07, Streptomyces, 67–14, SBR1031 and KD4-96 were the unique dominant genera in the L treatment. In contrast, FCPS473, Actinospica, 1921–2, Sinomonas, and Ktedonobacteraceae were the unique dominant genera in the CK treatment. The findings suggest that soil fertility all could be changed by different N application levels, but the most increasing integral effect only could be found in L. Moreover, even though soil bacterial richness could be significantly promoted by the M and H treatments, but soil bacterial diversity could not be significantly improved. On the contrary, soil bacterial diversity and richness all could be improved by L treatment. In addition, higher abundance of unique soil dominant bacteria could be only found in L treatment which compared to the CK, M and H treatments. These findings suggest that the rate of 96 kg ha−1 N application is ecofriendly for sugarcane production in Guangxi.
Small molecule targeting amyloid fibrils inhibits Streptococcus mutans biofilm formation
Authors: Chen Yuanyuan , Cui Guxin , Cui Yuqi , Chen Dongru , Lin Huancai
Published: December 2021

Amyloid fibrils are important scaffold in bacterial biofilms. Streptococcus mutans is an established cariogenic bacteria dwelling within biofilms, and C123 segment of P1 protein is known to form amyloid fibrils in S. mutans biofilms, among which C3 segment could serve as a promising anti-amyloid target due to its critical role in C123-P1 interactions. Recently, small molecules have been found to successfully inhibit biofilms by targeting amyloid fibrils. Thus, our study aimed to screen small molecules targeting C3 segment with the capacity to influence amyloid fibrils and S. mutans biofilms. In silico screening was utilized to discover promising small molecules, which were evaluated for their effects on bacterial cells and amyloid fibrils. We selected 99 small molecules and enrolled 55 small molecules named D1–D55 for crystal violet staining. Notably, D25 selectively inhibit S. mutans biofilms but had no significant influence on biofilms formed by Streptococcus gordonii and Streptococcus sanguinis, and D25 showed no bactericidal effects and low cytotoxicity. In addition, amyloid fibrils in free-floating bacteria, biofilms and purified C123 were quantified with ThT assays, and the differences were not statistically significant in the presence or absence of D25. Morphological changes of amyloid fibrils were visualized with TEM images, where amorphous aggregates were obvious coupled with long and atypical amyloid fibrils. Moreover, amyloid-related genes were upregulated in response to D25. In conclusion, D25 is a promising antimicrobial agent with the capacity to influence amyloid fibrils and inhibit S. mutans biofilms.
Proportional assist ventilation relieves clinically significant dyspnea in critically ill ventilated patients
Authors: Bureau Côme , Decavèle Maxens , Campion Sébastien , Nierat Marie-Cécile , Mayaux Julien , Morawiec Elise , Raux Mathieu , Similowski Thomas , Demoule Alexandre
Published: December 2021

Introduction

Dyspnea is common and often severe symptom in mechanically ventilated patients. Proportional assist ventilation (PAV) is an assist ventilatory mode that adjusts the level of assistance to the activity of respiratory muscles. We hypothesized that PAV reduce dyspnea compared to pressure support ventilation (PSV).

Patients and methods

Mechanically ventilated patients with clinically significant dyspnea were included. Dyspnea intensity was assessed by the Dyspnea—Visual Analog Scale (D-VAS) and the Intensive Care-Respiratory Distress Observation Scale (IC-RDOS) at inclusion (PSV-Baseline), after personalization of ventilator settings in order to minimize dyspnea (PSV-Personalization), and after switch to PAV. Respiratory drive was assessed by record of electromyographic activity of inspiratory muscles, the proportion of asynchrony was analyzed.

Results

Thirty-four patients were included (73% males, median age of 66 [57–77] years). The D-VAS score was lower with PSV-Personalization (37 mm [20‒55]) and PAV (31 mm [14‒45]) than with PSV-Baseline (62 mm [28‒76]) (p < 0.05). The IC-RDOS score was lower with PAV (4.2 [2.4‒4.7]) and PSV-Personalization (4.4 [2.4‒4.9]) than with PSV-Baseline (4.8 [4.1‒6.5]) (p < 0.05). The electromyographic activity of parasternal intercostal muscles was lower with PAV and PSV-Personalization than with PSV-Baseline. The asynchrony index was lower with PAV (0% [0‒0.55]) than with PSV-Baseline and PSV-Personalization (0.68% [0‒2.28] and 0.60% [0.31‒1.41], respectively) (p < 0.05).

Conclusion

In mechanically ventilated patients exhibiting clinically significant dyspnea with PSV, personalization of PSV settings and PAV results in not different decreased dyspnea and activity of muscles to a similar degree, even though PAV was able to reduce asynchrony more effectively.
Risk perception and psychological state of healthcare workers in referral hospitals during the early phase of the COVID-19 pandemic, Uganda
Authors: Migisha Richard , Ario Alex Riolexus , Kwesiga Benon , Bulage Lilian , Kadobera Daniel , Kabwama Steven N. , Katana Elizabeth , Ndyabakira Alex , Wadunde Ignatius , Byaruhanga Aggrey , Amanya Geofrey , Harris Julie R. , Fitzmaurice Arthur G.
Published: December 2021

Background

Safeguarding the psychological well-being of healthcare workers (HCWs) is crucial to ensuring sustainability and quality of healthcare services. During the COVID-19 pandemic, HCWs may be subject to excessive mental stress. We assessed the risk perception and immediate psychological state of HCWs early in the pandemic in referral hospitals involved in the management of COVID-19 patients in Uganda.

Methods

We conducted a cross-sectional survey in five referral hospitals from April 20–May 22, 2020. During this time, we distributed paper-based, self-administered questionnaires to all consenting HCWs on day shifts. The questionnaire included questions on socio-demographics, occupational behaviors, potential perceived risks, and psychological distress. We assessed risk perception towards COVID-19 using 27 concern statements with a four-point Likert scale. We defined psychological distress as a total score > 12 from the 12-item Goldberg’s General Health Questionnaire (GHQ-12). We used modified Poisson regression to identify factors associated with psychological distress.

Results

Among 335 HCWs who received questionnaires, 328 (98%) responded. Respondents’ mean age was 36 (range 18–59) years; 172 (52%) were male. The median duration of professional experience was eight (range 1–35) years; 208 (63%) worked more than 40 h per week; 116 (35%) were nurses, 52 (14%) doctors, 30 (9%) clinical officers, and 86 (26%) support staff. One hundred and forty-four (44%) had a GHQ-12 score > 12. The most common concerns reported included fear of infection at the workplace (81%), stigma from colleagues (79%), lack of workplace support (63%), and inadequate availability of personal protective equipment (PPE) (56%). In multivariable analysis, moderate (adjusted prevalence ratio, [aPR] = 2.2, 95% confidence interval [CI] 1.2–4.0) and high (aPR = 3.8, 95% CI 2.0–7.0) risk perception towards COVID-19 (compared with low-risk perception) were associated with psychological distress.

Conclusions

Forty-four percent of HCWs surveyed in hospitals treating COVID-19 patients during the early COVID-19 epidemic in Uganda reported psychological distress related to fear of infection, stigma, and inadequate PPE. Higher perceived personal risk towards COVID-19 was associated with increased psychological distress. To optimize patient care during the pandemic and future outbreaks, workplace management may consider identifying and addressing HCW concerns, ensuring sufficient PPE and training, and reducing infection-associated stigma.
Poor glycemic control enhances the disease activity in the RA patients with undiagnosed diabetes—a cross-sectional clinical study
Authors: Palit Pulak Kanti , Islam Ashekul , Habib Md Syeed Al , Mujib Abu Syed Mohammed , Datta Joyonti , Chakraborty Bahni , Dhar Suman , Chowdhury Dhiman , Chowdhury Md Faisal Fahad , Ali Mohammad Shawkat , Yesmin Arfana , Islam Mohammod Johirul , Akther Nishat , Al Mamun Abdullah , Islam Khairul , Nath Pradip Kumar
Published: December 2021

Background

Rheumatoid arthritis (RA), an autoimmune disorder, characterized by systemic inflammation and swollen joints, establishes itself as a critical threat. A pro-inflammatory cytokine TNF-α is a well-known driver of RA pathogenesis and at the same time predisposes to insulin resistance through signal impediment which ultimately paves the way for type 2 diabetes (T2DM). However, in patients with RA, T2DM remains significantly undiagnosed or undertreated, apparently which increases the risk of developing cardio-metabolic comorbidities. This study aimed to evaluate the glycemic status among RA patients and its association with disease activity.

Result

One hundred fifty inpatients RA cases according to ACR/EULAR standards were included in the cross-sectional study who have an average age of 45.4±12.15 years and a median and interquartile period of RA of 2.25 years and 0.48–6 years, respectively. We discovered that 36% of people had T2DM, 26% were prediabetic, and 38% were non-diabetic. Age was shown to be significantly correlated with DM frequency in RA patients (p=0.007). There were 28 patients with elevated disease activity (19%) and 60 patients with low disease activity (40%) in this study. No substantial associations were found in the presence of DM with gender, anti-CCP, RF, disease duration, or DAS28.

Conclusion

RA patients are more likely to experience diabetes, and resultantly a high index of notion must be kept. Clinician should be aware about the affliction of undiagnosed diabetes and prediabetes in RA patients. Furthermore, keeping an eye on glycemic control in RA patients could prevent metabolic and cardiovascular comorbidities in those susceptible patients.
Headspace for parents: qualitative report investigating the use of a mindfulness-based app for managing parents’ stress during COVID-19
Authors: Burgess Abigail , Cavanagh Kate , Strauss Clara , Oliver Bonamy R.
Published: December 2021

Background

Stress can compromise parental well-being and may contribute to harsh and critical parenting styles, which are in turn associated with children's conduct problems. Coronavirus disease 2019 (COVID-19)-related restrictions are likely to have exacerbated parental stress as, for many, UK-based family life was altered considerably. Mindfulness has been demonstrated to improve stress management and emotion regulation when delivered to parents in person, however, more accessible online interventions are under-researched.

Aims

To provide preliminary data on family well-being and parent–child relationships as well as the acceptability and usability of the Headspace app – a self-delivered mindfulness-based intervention – for parents in low-risk families during the early days of the COVID-19 pandemic.

Method

We provided 12 parents with access to Headspace, and collected qualitative data (semi-structured interviews and 5 minute speech samples) immediately following the initial COVID-19 lockdown in the UK. The resulting transcripts were thematically analysed.

Results

Most parents reported Headspace to be acceptable and useful – improvements in parents’ own sleep were particularly noted – and there was high adherence to the intervention. However, difficulties related to family well-being and parent–child relationships following the lockdown were also reported.

Conclusions

As a result of the confounding impact of COVID-19 restrictions, and varied access to app content, we were unable to determine any outcomes to be a result of practising mindfulness specifically. However, COVID-19 has had a profound impact on many UK-based families, including those previously at low risk, and our results demonstrate that Headspace may have beneficial effects for parents. There is a need to more rigorously test this tool with a broader range of families.