bluuebunny/crossref_metadata_2025 huggingface dataset:
The best postoperative adjuvant therapy for patients with early stage cervical adenosquamous carcinoma
Authors: Liu Yawen , Tu Haiyan , Zhang Lingling , Zhong Meiling , Wang Yanan , Li Ling , Xiang Xiaojun
Published: April 2022

Background

Cervical adenosquamous carcinoma (ASC) was previously thought to be a subtype of cervical adenocarcinoma, but recent studies have found that the clinical features of the two diseases are different. Moreover, the pathological characteristics, survival, prognosis, and optimal ASC therapy remain unknown. This study aims to retrospectively analyze the postoperative survival of patients with early-stage ASC and to evaluate their condition after treatment with postoperative concurrent chemoradiotherapy (CCRT) and prophylactic irradiation of the para-aortic lymphatic drainage area.

Methods

This study enrolled 131 patients with pathologically confirmed ASC screened from 3502 patients with confirmed stage I–II cervical cancer diagnosis who had completed surgical treatments in our hospital. Among the 131 enrolled patients, 75 patients received CCRT, 33 patients received chemotherapy (CT), and 23 patients did not receive adjuvant treatment (named surgery alone (S alone). Of the 75 patients CCRT, 43 patients received prophylactic irradiation of the para-aortic lymphatic drainage area. The efficacy of the postoperative treatments of patients among groups (CCRT, CT, and S alone) was compared.

Results

The median follow-up time, age, and overall survival (OS) were 76 months, 43 years, and 74 months, respectively. The 3- and 5-year survival rates were 82% and 71.4%, respectively. The median disease-free survival (DFS) was 64 months. Cox regression analysis showed that postoperative adjuvant treatment modalities and positive lymph node metastases were associated with OS and DFS. Patients who received CCRT treatment had higher OS and DFS than those with CT and S alone. Prophylactic irradiation of the para-aortic lymphatic drainage area did not improve the OS and DFS of patients with CCRT treatment. However, further subgroup analysis suggested that it might improve survival rates in patients who had positive pelvic lymph nodes as confirmed by postoperative pathology.

Conclusion

Postoperative CCRT improved the survival rates in patients with early-stage ASC. The value of prophylactic irradiation of the para-aortic lymphatic drainage area remains debatable, but it may benefit patients with pelvic lymph node involvement.
Post Laparoscopy Pain Reduction Project I (POLYPREP I): intraperitoneal normal saline instillation—a randomised controlled trial
Authors: Adlan Aizura Syafinaz Ahmad , Azhary Jerilee Mariam Khong , Tarmidzi Hairel Zulhamdi Mohd , Kamarudin Maherah , Lim Raymond Chung Siang , Ng Doris Sin Wen
Published: April 2022

Objectives

To evaluate the effect of intraperitoneal normal saline instillation (INSI) of 15 mL/kg body weight on postoperative pain after a gynaecological laparoscopic procedure.

Design

Randomised controlled trial.

Setting

University Hospital in Kuala Lumpur, Malaysia.

Participants

Patients aged 18–55 years, with American Society of Anaesthesiologists (ASA) classification I–II, scheduled for an elective gynaecological laparoscopic procedure for a benign cause.

Intervention

The patients were randomly allocated to two groups. In the intervention group, 15 mL/kg body weight of normal saline was instilled intraperitoneally, while the control group received the conventional combination of open laparoscopic trocar valves with gentle abdominal pressure to remove the retained carbon dioxide.

Main outcome measures

The outcomes measured were the mean pain scores for shoulder and upper abdominal pain at 24 h, 48 h, and 72 h postoperatively.

Results

A total of 68 women completed the study, including 34 women in each group. There was no difference in the shoulder pain score at 24 h, 48 h, and 72 h postoperatively. However, a significant improvement in the upper abdominal pain score after 48 h (95% confidence interval [CI] 0.34–1.52, p = 0.019) and 72 h (95% CI 0.19–0.26, p = 0.007) postoperatively were observed.

Conclusions

INSI of 15 mL/kg body weight does not lower postoperative shoulder pain compared to no fluid instillation. A modest pain score improvement was observed in the upper abdominal area at 48 h and 72 h after surgery. An INSI of up to 30 mL/kg body weight may be required to eliminate shoulder pain. Care must be taken before administering a higher amount of INSI, considering the potential risk of peritoneal adhesions.

Clinical registration ISRCTN Identifier: 87898051 (Date: 26 June 2019) https://doi.org/10.1186/ISRCTN87898051
Teaching design thinking as a tool to address complex public health challenges in public health students: a case study
Authors: Ingram Carolyn , Langhans Tessa , Perrotta Carla
Published: April 2022

Background

Developing a public health workforce that can understand problems from a population perspective is essential in the design of impactful user-centred responses to current population health challenges. Design Thinking, a user-driven process for problem-defining and solution-finding, not only has utility in the field of public health but stands as a potential mechanism for developing critical skills -such as empathy, creativity and innovation- amongst future professionals. Though the literature reflects the use of DT across many health sciences disciplines, less research has been published on how students apply learned concepts using real-world challenges of their choice and what difficulties they face during the process.

Methods

This case study evaluates achieved learning outcomes after the introduction of a design thinking block into post-graduate public health curriculum at the University College Dublin. Two independent assessors evaluated student learning outcomes and observed difficulties during the process by assessing group presentations to identify and understand any learning difficulties using an ad-hoc designed tool. The tool consisted of twelve items scored using a 5-point Likert scale. Student feedback, in the form of an online survey, was also analysed to determine their level of enjoyment, perceived learning outcomes and opinions on the course content.

Results

The assessors evaluated thirteen DT group presentations and reports from 50 students. The groups chose a range of topics from socialization of college students during Covid-19 to mental health challenges in a low-income country. Independent assessment of assignments revealed that the highest scores were reached by groups who explored a challenge relevant to their own lives (more than 80% of total possible points versus 60% class average). The groups that explored challenges more distant to themselves struggled with problem finding with a mean score of 2.05 (SD ± 1.2) out of 5 in that domain. The greatest difficulties were observed in problem finding and ideation. Though most students found the design thinking block enjoyable and relevant to their education, they recommended that the DT block be a stand-alone module. Students recognized that groups who chose a familiar topic experienced fewer difficulties throughout the process.

Conclusion

The study showed that DT learning outcomes were best achieved when students focused on challenges, they had either personally experienced or were familiar with. These findings provide insight for future iterations of DT workshops and support the teaching of user-centred approaches to future public health practitioners.
The influence of non-clinical pharmacists’ understanding of and attitudes towards pharmaceutical care on their willingness to serve as clinical pharmacists in China
Authors: Wan Chuchuan , Huang Yuankai , Chen Lei , Xi Xiaoyu
Published: April 2022

Background

The shortage of clinical pharmacists is severe in China, and transferring non-clinical pharmacists into clinical pharmacists serves as a feasible solution to this problem. In China, a one-year training programme is available for non-clinical pharmacists, and those who have finished the programme are certificated as clinical pharmacists. However, not all non-clinical pharmacists are willing to serve as clinical pharmacists, and their willingness to serve as clinical pharmacists may be related to their attitudes towards pharmaceutical care. This study aims to test whether non-clinical pharmacists’ attitudes towards pharmaceutical care is positively correlated with their willingness to serve as clinical pharmacists.

Methods

A cross-sectional survey was conducted in secondary and tertiary hospitals in China to collect non-clinical pharmacists’ basic demographic information, attitudes towards pharmaceutical care and willingness to serve as clinical pharmacists. An ordered logistic regression analysis was performed to test the relationship between non-clinical pharmacists’ attitudes towards pharmaceutical care and their willingness to serve as clinical pharmacists.

Results

One thousand five hundred eighty non-clinical pharmacists from 755 hospitals were invited to participate in the study. Finally, 1308 valid responses were obtained and the response rate reached 82.78%. The regression results (R2 = 0.052, chi-square = 174.024,p < 0.0001) suggested that attitudes towards pharmaceutical care had a positive impact on non-clinical pharmacists’ willingness to serve as clinical pharmacists (p < 0.01). Control variables, such as age (p < 0.05), marital status (p < 0.05), professional title (p < 0.1), educational level (p < 0.1), salary expectations (p < 0.01) and experience providing pharmaceutical care (p < 0.01), also influenced non-clinical pharmacists’ willingness to serve as clinical pharmacists.

Conclusions

Based on the results, suggestions are made to increase non-clinical pharmacists’ willingness to serve as clinical pharmacists.
Improving public health sector service delivery in the Free State, South Africa: development of a provincial intervention model
Authors: Malakoane Benjamin , Heunis James Christoffel , Chikobvu Perpetual , Kigozi Nanteza Gladys , Kruger Willem Hendrik
Published: April 2022

Background

Public health sector service delivery challenges leading to poor population health outcomes have been observed in the Free State province of South Africa for the past decade. A multi-method situation appraisal of the different functional domains revealed serious health system deficiencies and operational defects, notably fragmentation of healthcare programmes and frontline services, as well as challenges related to governance, accountability and human resources for health. It was therefore necessary to develop a system-wide intervention to comprehensively address defects in the operation of the public health system and its major components.

Methods

This study describes the development of the ‘Health Systems Governance & Accountability’ (HSGA) intervention model by the Free State Department of Health (FSDoH) in collaboration with the community and other stakeholders following a participatory action approach. Documented information collected during routine management processes were reviewed for this paper. Starting in March 2013, the development of the HSGA intervention model and the concomitant application of Kaplan and Norton’s (1992) Balanced Scorecard performance measurement tool was informed by the World Health Organization’s (2007) conceptual framework for health system strengthening and reform comprised of six health system ‘building blocks.’ The multiple and overlapping processes and actions to develop the intervention are described according to the four steps in Kaplan et al.’s (2013) systems approach to health systems strengthening: (i) problem identification, (ii) description, (iii) alteration and (iv) implementation.

Results

The finalisation of the HSGA intervention model before end-2013 was a prelude to the development of the FSDoH’s Strategic Transformation Plan 2015–2030. The HSGA intervention model was used as a tool to implement and integrate the Plan’s programmes moving forward with a consistent focus on the six building blocks for health systems strengthening and the all-important linkages between them.

Conclusion

The model was developed to address fragmentation and improve public health service delivery by the provincial health department. In January 2016, the intervention model became an official departmental policy, meaning that it was approved for implementation, compliance, monitoring and reporting, and became the guiding framework for health systems strengthening and transform in the Free State.
Implementing the right care in the right place at the right time for non-alcoholic fatty liver disease (NAFLD-RRR study): a study protocol for a community care pathway for people with type 2 diabetes
Authors: Gracen Lucy , Hayward Kelly L. , Aikebuse Melanie , Russell Anthony , O’Beirne James , McPhail Steven , Irvine Katharine M. , Williams Suzanne , Valery Patricia C. , Powell Elizabeth E.
Published: April 2022

Background

Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic that affects approximately half of all people with type 2 diabetes. Those with type 2 diabetes are a high-risk NAFLD subgroup because of their increased risk of clinically significant liver-related outcomes from NAFLD which include hepatocellular carcinoma, cirrhosis-related complications and liver disease mortality. They may benefit from early detection of disease as this would allow at risk patients to access hepatocellular carcinoma surveillance, emerging drug trials for NAFLD and specialist hepatology care prior to emergence of liver-related complications.

Methods

This is a prospective cohort study aimed at incorporating and assessing a community care pathway for liver fibrosis screening into routine care for type 2 diabetes. Patients undergo a point of care assessment of hepatic steatosis and stiffness using FibroScan at the time of the routine diabetes appointment or when attending the clinic for blood tests in preparation for this appointment.

Discussion

We propose that implementation of a community-based NAFLD diagnosis, risk-stratification, and referral pathway for people with type 2 diabetes is feasible, will provide earlier, targeted detection of advanced fibrosis, and reduce unnecessary referrals to hepatology outpatients for fibrosis risk assessment. Our study will provide important information about the feasibility of establishing a NAFLD pathway for people with type 2 diabetes in primary care. Ultimately, our findings will help direct spending and resource allocation for NAFLD in a high-risk population. Regular evaluation by stakeholders during implementation will help to create a reliable and sustainable community care pathway and establish a perpetual cycle of learning in primary care.

Trial registration

ANZCTR, ACTRN12621000330842. Registered 23 March 2021.
Affordable Care Act Medicaid expansion and access to primary-care based smoking cessation assistance among cancer survivors: an observational cohort study
Authors: Bailey Steffani R. , Voss Robert , Angier Heather , Huguet Nathalie , Marino Miguel , Valenzuela Steele H. , Chung-Bridges Katherine , DeVoe Jennifer E.
Published: April 2022

Background

Smoking among cancer survivors can increase the risk of cancer reoccurrence, reduce treatment effectiveness and decrease quality of life. Cancer survivors without health insurance have higher rates of smoking and decreased probability of quitting smoking than cancer survivors with health insurance. This study examines the associations of the Affordable Care Act (ACA) Medicaid insurance expansion with smoking cessation assistance and quitting smoking among cancer survivors seen in community health centers (CHCs).

Methods

Using electronic health record data from 337 primary care community health centers in 12 states that expanded Medicaid eligibility and 273 CHCs in 8 states that did not expand, we identified adult cancer survivors with a smoking status indicating current smoking within 6 months prior to ACA expansion in 2014 and ≥ 1 visit with smoking status assessed within 24-months post-expansion. Using an observational cohort propensity score weighted approach and logistic generalized estimating equation regression, we compared odds of quitting smoking, having a cessation medication ordered, and having ≥6 visits within the post-expansion period among cancer survivors in Medicaid expansion versus non-expansion states.

Results

Cancer survivors in expansion states had higher odds of having a smoking cessation medication order (adjusted odds ratio [aOR] = 2.54, 95%CI = 1.61-4.03) and higher odds of having ≥6 office visits than those in non-expansion states (aOR = 1.82, 95%CI = 1.22-2.73). Odds of quitting smoking did not differ significantly between patients in Medicaid expansion versus non-expansion states.

Conclusions

The increased odds of having a smoking cessation medication order among cancer survivors seen in Medicaid expansion states compared with those seen in non-expansion states provides evidence of the importance of health insurance coverage in accessing evidence-based tobacco treatment within CHCs. Continued research is needed to understand why, despite increased odds of having a cessation medication prescribed, odds of quitting smoking were not significantly higher among cancer survivors in Medicaid expansion states compared to non-expansion states.
Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones
Authors: Karademir Duygu , Todorova Vyara , Ebner Lynn J. A. , Samardzija Marijana , Grimm Christian
Published: April 2022

Background

In inherited retinal disorders such as retinitis pigmentosa (RP), rod photoreceptor-specific mutations cause primary rod degeneration that is followed by secondary cone death and loss of high-acuity vision. Mechanistic studies of retinal degeneration are challenging because of retinal heterogeneity. Moreover, the detection of early cone responses to rod death is especially difficult due to the paucity of cones in the retina. To resolve heterogeneity in the degenerating retina and investigate events in both types of photoreceptors during primary rod degeneration, we utilized droplet-based single-cell RNA sequencing in an RP mouse model,rd10.

Results

Using trajectory analysis, we defined two consecutive phases of rod degeneration at P21, characterized by the early transient upregulation ofEgr1and the later induction ofCebpd. EGR1 was the transcription factor most significantly associated with the promoters of differentially regulated genes inEgr1-positive rods in silico. SilencingEgr1affected the expression levels of two of these genes in vitro. Degenerating rods exhibited changes associated with metabolism, neuroprotection, and modifications to synapses and microtubules.Egr1was also the most strongly upregulated transcript in cones. Its upregulation in cones accompanied potential early respiratory dysfunction and changes in signaling pathways. The expression pattern of EGR1 in the retina was dynamic during degeneration, with a transient increase of EGR1 immunoreactivity in both rods and cones during the early stages of their degenerative processes.

Conclusion

Our results identify early and late changes in degeneratingrd10rod photoreceptors and reveal early responses to rod degeneration in cones not expressing the disease-causing mutation, pointing to mechanisms relevant for secondary cone degeneration. In addition, our data implicate EGR1 as a potential key regulator of early degenerative events in rods and cones, providing a potential broad target for modulating photoreceptor degeneration.
Bacterial and parasite co-infection in Mexican golden trout (Oncorhynchus chrysogaster) by Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator
Authors: Fuentes-Valencia María Anel , Osornio-Esquivel José Luis , Martínez Palacios Carlos Antonio , Contreras-Ávila José Luis , Barriga-Tovar Erik , la Mora Genoveva Ingle-de , Arellano-Torres Andrés , Baizabal-Aguirre Víctor Manuel , Bravo-Patiño Alejandro , Cajero-Juárez Marcos , Valdez Alarcón Juan José
Published: April 2022

Background

Bacterial infections are responsible of high economic losses in aquaculture. Mexican golden trout (Oncorhynchus chrysogaster) is a threatened native trout species that has been introduced in aquaculture both for species conservation and breeding for production and for which no studies of bacterial infections have been reported.

Case presentation

Fish from juvenile stages of Mexican golden trout showed an infectious outbreak in a farm in co-culture with rainbow trout (Oncorhynchus mykiss), showing external puntiform red lesions around the mouth and caudal pedunculus resembling furuncles by Aeromonas spp. and causing an accumulated mortality of 91%. Isolation and molecular identification of bacteria from lesions and internal organs showed the presence of Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator isolated from a single individual. All bacterial isolates were resistant to amoxicillin-clavulanic acid and cefazoline. P. shigelloides was resistant to third generation β-lactamics.

Conclusions

This is the first report of coinfection by Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator in an individual of Mexican golden trout in co-culture with rainbow trout. Resistance to β-lactams suggests the acquisition of genetic determinants from water contamination by human- or livestock-associated activities.
Do state laws reduce uptake of Medicaid/CHIP by U.S. citizen children in immigrant families: evaluating evidence for a chilling effect
Authors: Twersky Sylvia E.
Published: April 2022

Background

Restrictive state laws aimed at immigrants can have unintended consequences for health insurance coverage of United States citizens in immigrant families due to both actual barriers created by the laws and perceived barriers among immigrants. Increasing numbers of children in the U.S. are part of immigrant families, and these children are more likely to be living in poverty than their counterparts in native families. Immigrant restrictive policies could lead to reduced access to Medicaid and CHIP even for citizen children in immigrant families.

Methods

Using data from the Current Population Survey's (CPS) March Supplement, linear probability models with difference-in-differences (DD) estimates compare probability of enrollment in Medicaid/CHIP among low-income U.S. citizen children in immigrant families and low-income children in native families and U.S. citizen children in immigrant families in states that did not adopt restrictive legislation, in order to estimate the impact of restrictive state laws aimed at immigrants. An additional model explores the effect of mother’s citizenship on enrollment among all immigrant families in states with and without restrictive legislation.

Results

Results suggest a significant chilling effect where the magnitude of the effect varies according to family demographics and by the types of laws being passed. Immigrant restrictive social welfare laws being adopted have a strong negative effect on U.S. citizen children in immigrant families’ enrollment in Medicaid/CHIP, a 5.5 percentage point reduction in coverage. Among the subsample of only immigrant families, results point toward a global chilling effect created by an overall restrictive policy environment. All immigrant restrictive related laws, including those aimed at education, job restriction, identification access, and social welfare restrictions have a significant and negative impact on access to public insurance for U.S. citizen children with non-citizen mothers.

Conclusions

This research shows that the unintended consequence of restrictive state legislation aimed at immigrants is the reduction in access to Medicaid and CHIP by low-income U.S. citizen children living in immigrant families. Reduced access to health insurance can increase unmet medical needs for an already vulnerable group.
Double-activation of mitochondrial permeability transition pore opening via calcium overload and reactive oxygen species for cancer therapy
Authors: Zhou Ying , Jing Shisong , Liu Sainan , Shen Xizhong , Cai Lihan , Zhu Changfeng , Zhao Yicheng , Pang Maolin
Published: April 2022

Background

Calcium ions (Ca2+) participates in various intracellular signal cascades and especially plays a key role in pathways relevant to cancer cells. Mitochondrial metabolism stimulated by calcium overload can trigger the opening of the mitochondrial permeability transition pore (MPTP), which leads to cancer cell death.

Methods

Herein, a mitochondrial pathway for tumour growth inhibition was built via the double-activation of MPTP channel. Fe2+ doped covalent organic frameworks (COF) was synthesised and applied as template to grow CaCO3 shell. Then O2 was storaged into Fe2+ doped COF, forming O2-FeCOF@CaCO3 nanocomposite. After modification with folic acid (FA), O2-FeCOF@CaCO3@FA (OFCCF) can target breast cancer cells and realize PDT/Ca2+ overload synergistic treatment.

Results

COF can induce the production of 1O2 under 650 nm irradiation for photodynamic therapy (PDT). Low pH and hypoxia in tumour microenvironment (TME) can activate the nanocomposite to release oxygen and Ca2+. The released O2 can alleviate hypoxia in TME, thus enhancing the efficiency of COF-mediated PDT. Abundant Ca2+ were released and accumulated in cancer cells, resulting in Ca2+ overload. Notably, the reactive oxygen species (ROS) and Ca2+ overload ensure the sustained opening of MPTP, which leads to the change of mitochondria transmembrane potential, the release of cytochrome c (Cyt c) and the activation of caspases 3 for cancer cell apoptosis.

Conclusion

This multifunctional nanosystem with TME responded abilities provided a novel strategy for innovative clinical cancer therapy.

Graphical Abstract
Different phases of ATS use call for different interventions: a large qualitative study in Europe
Authors: Liebregts Nienke , Rigoni Rafaela , Petruželka Benjamin , Barták Miroslav , Rowicka Magdalena , Zurhold Heike , Schiffer Katrin
Published: April 2022

Background

Amphetamine-type stimulants (ATS) are globally widely used. Scientific literature generally defines four phases of substance use (initiation, continuation, increase and decrease); however, there is limited understanding of what influences these different phases of ATS use. The ATTUNE study investigated which factors shape individual phases of use, or ATS use patterns. In this article, we report on these phases into and out of ATS use, and propose a set of recommendations for prevention, harm reduction and treatment of the different phases of ATS use.

Methods

Qualitative, semi-structured interviews (n = 237) were conducted in five different European countries with participants who had used ATS, varying from a few times in a lifetime to daily.

Results

Amphetamine and MDMA were the most commonly used ATS. Yet, types of ATS used differed between the countries. We found that people who use ATS have various motives for and dynamic patterns of ATS use with alternating phases of increase, continuation, decrease and sometimes dependence. Cessation was pursued in different ways and for diverse reasons, such as mental health problems and maturing out. Availability seemed not an issue, regardless of the type of ATS, phase or country.

Conclusions

These findings demonstrate that tailor-made interventions are needed for the diverse types of people who use ATS and different phases or patterns of ATS use, to reduce possible harms of use. We recommended a set of interventions for the different ATS phases. These include drug checking services, peer-led information, self-management of ATS use, mental health support to help people cope with stressful life events and prevent uncontrolled use, and follow-up support after treatment.
Transition readiness in adolescents and young adults with chronic rheumatic disease in Oman: today’s needs and future challenges
Authors: Abdwani Reem , Al Sabri Rumaitha , Al Hasni Zawan , Rizvi Seyad , Al Wahshi Humaid , Al Lawati Batool , Al Abrawi Safiya , Wali Yassir , Al Sadoon Mona
Published: April 2022

Introduction

In Oman, the ““transition” of health care of adolescents to adult care occurs at a young age, like many other GCC countries for cultural reasons. In order to address this concern, this study was conducted to determine the transition readiness skills of adolescents and young adults with childhood onset rheumatic diseases using a cross-cultural adaptation of the UNC TRxANSITION scale.

Methods

We used a professionally translated/back translated, provider-administered UNC TRxANSITION Scale. This 32-question scale measures HCT in 10 domains including knowledge about diagnosis or treatment, diet, reproductive health, school/work, insurance, ability to self-manage and identification of new health providers. The maximum transitional score of 10, was categorized as low (1-4), moderate (4 - 7) and high (7 -10) transitional readiness scores.

Results

We enrolled 81 Omani adolescents and young adults (AYA) with chronic childhood onset rheumatic diseases. The cohort consisted of 79% females, with mean age of 15.8 years (± 3.53) and mean disease duration of 6.95 years (± 4.83). Our cohort’s overall mean score is low 5.22 (±1.68). Only 14.8% of the cohort achieved a high transition score (≥7). Significant direct relationship was observed between age and the mean transition readiness score (r = .533,P < .001). The mean transition readiness score in the younger age group (10-13 years) was 4.07 (±1.29), the middle age group (14-18 years) was 5.43 (±1.27), while the older age group (19-21 year), was 6.12 (±1.81). Mean transition score of youngest age group was found to be significantly lower than the other two age groups (p = .003).

Conclusion

Overall, the transition readiness of AYA in Oman is low compared to other western countries indicating the need to initiate a health care transition preparation program for patients with chronic diseases across the country. In addition, we need to establish regional guidelines to address the transfer and transition policies to be in line to international recommendations.

As transition continues after transfer, and is preferably guided by adolescent developmental status rather than chronological age, it would be preferable to refer to the transition and transfer policies 9rather than transitional age policy) to be in line to international recommendations.
Synaptic loss and progression in mice infected with Angiostrongylus cantonensis in the early stage
Authors: Jhan Kai-Yuan , Chang Pi-Kai , Cheng Chien-Ju , Jung Shih-Ming , Wang Lian-Chen
Published: April 2022

Background

Angiostrongylus cantonensis is also known as rat lungworm. Infection with this parasite is a zoonosis that can cause eosinophilic meningitis and/or eosinophilic meningoencephalitis in humans and may lead to fatal outcomes in severe cases. In this study, we explored the mechanisms of the impairments in the cognitive functions of mice infected with A. cantonensis.

Methods

In infected mice with different infective intensities at different timepoint postinfection, loss and recovery of cognitive functions such as learning and memory abilities were determined. Neuronal death and damage to synaptic structures were analyzed by Western blotting and IHC in infected mice with different infection intensities at different timepoint postinfection.

Results

The results of behavioral tests, pathological examinations, and Golgi staining showed that nerve damage caused by infection in mice occurred earlier than pathological changes of the brain. BDNF was expressed on 14 day post-infection. Cleaved caspase-3 increased significantly in the late stage of infection. However, IHC on NeuN indicated that no significant changes in the number of neurons were found between the infected and uninfected groups.

Conclusions

The synaptic loss caused by the infection of A. cantonensis provides a possible explanation for the impairment of cognitive functions in mice. The loss of cognitive functions may occur before severe immunological and pathological changes in the infected host.
The smoothened agonist SAG reduces mitochondrial dysfunction and neurotoxicity of frataxin-deficient astrocytes
Authors: Vicente-Acosta Andrés , Giménez-Cassina Alfredo , Díaz-Nido Javier , Loria Frida
Published: April 2022

Background

Friedreich’s ataxia is a rare hereditary neurodegenerative disease caused by decreased levels of the mitochondrial protein frataxin. Similar to other neurodegenerative pathologies, previous studies suggested that astrocytes might contribute to the progression of the disease. To fully understand the mechanisms underlying neurodegeneration in Friedreich’s ataxia, we investigated the reactivity status and functioning of cultured human astrocytes after frataxin depletion using an RNA interference-based approach and tested the effect of pharmacologically modulating the SHH pathway as a novel neuroprotective strategy.

Results

We observed loss of cell viability, mitochondrial alterations, increased autophagy and lipid accumulation in cultured astrocytes upon frataxin depletion. Besides, frataxin-deficient cells show higher expression of several A1-reactivity markers and release of pro-inflammatory cytokines. Interestingly, most of these defects were prevented by chronically treating the cells with the smoothened agonist SAG. Furthermore, in vitro culture of neurons with conditioned medium from frataxin-deficient astrocytes results in a reduction of neuronal survival, neurite length and synapse formation. However, when frataxin-deficient astrocytes were chronically treated with SAG, we did not observe these alterations in neurons.

Conclusions

Our results demonstrate that the pharmacological activation of the SHH pathway could be used as a target to modulate astrocyte reactivity and neuron–glia interactions to prevent neurodegeneration in Friedreich’s ataxia.
The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion
Authors: Wu Mengliang , Downie Laura E. , Hill Lisa J. , Chinnery Holly R.
Published: April 2022

Background

Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration.

Methods

Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury.

Results

In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h.

Conclusions

Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (< 24 h), and inhibiting macrophage density at the study endpoint (5 days). These immunomodulatory effects were associated with faster re-epithelialisation and likely contribute to promoting sensory nerve regeneration. The findings suggest a potential interaction between DCs and neutrophils with topical decorin treatment, as the decorin-induced neutrophil inhibition was absent in Cx3cr1gfp/gfp mice that lack corneal epithelial DCs. TGF-β and CSPG4 proteoglycan likely regulate decorin-mediated innate immune cell responses and nerve regeneration after injury.
Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients
Authors: Nelke Christopher , Stascheit Frauke , Eckert Carmen , Pawlitzki Marc , Schroeter Christina B. , Huntemann Niklas , Mergenthaler Philipp , Arat Ercan , Öztürk Menekse , Foell Dirk , Schreiber Stefanie , Vielhaber Stefan , Gassa Asmae , Stetefeld Henning , Schroeter Michael , Berger Benjamin , Totzeck Andreas , Hagenacker Tim , Meuth Sven G. , Meisel Andreas , Wiendl Heinz , Ruck Tobias
Published: April 2022

Background

Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome.

Methods

We examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation.

Results

815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange.

Conclusions

MC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients.

Graphical Abstract
Comprehensive Medical Support in Complex Emergencies (CMSCE): pilot course review
Authors: Quinn John M , Jigar Trisha , Reinwald Michael , Annan Percy S T , Aapore Thomas , Wilson James M , Bourdeaux Margaret Ellis , Ulrichs Timo , Bricknell Martin CM , Moore Alan , Goebbels Stefan , Haggenmiller Christian
Published: April 2022

Global threats to health and health security are growing. Fragile and failed states, armed groups, ungoverned spaces, outbreaks and potential unknown “Disease X” threats, antimicrobial resistance (AMR), hybrid and gray zone conflict all exacerbate complex medical emergencies. These growing threats increase preventable morbidity and mortality of the most vulnerable populations. In an effort to promote best practices, standardize responses, and prevent excess death and disability in these contexts, The Kofi Annan International Peacekeeping Training Centre (KAIPTC), with support from multiple international partners and a volunteer facilitator faculty, administered the pilot course for military and civilian health officers involved in U.N. peacekeeping missions entitled, “Comprehensive Medical Support in Complex Emergencies (CMSCE 19).” This brief review paper provides a description of the process in designing and delivering an interdisciplinary course for providers and decision makers responding to complex emergencies. We conclude with best practices and next steps for course evolution.
Potential of RNA-binding protein human antigen R as a driver of osteogenic differentiation in osteoporosis
Authors: Liu Zelin , Li Baitao , Hu Hai , Li Xiaodong , Zhang Xiaofeng
Published: April 2022

Background

Emerging evidence has correlated the human antigen R (HuR) with the low-density lipoprotein receptor-related protein 6 (LRP6) gene, an important therapeutic target for osteoporosis. Herein, we sought to probe the regulatory role of HuR in the LRP6 gene and their interaction in the progression of osteoporosis.

Methods

HuR and downstream potential target genes were predicted by bioinformatics analysis to identify their potential functions in bone metabolism following osteoporosis. The effect of HuR on the osteoblastic differentiation and viability and apoptosis of mouse embryo osteoblast precursor cells (MC3T3-E1) was evaluated after artificial modulation of HuR expression.

Results

Bone phenotypes were observed in ovariectomized mice in response to adenovirus-mediated HuR overexpression. Poor expression of HuR was identified in the bone tissues of ovariectomized mice. Silencing of HuR inhibited the osteoblastic differentiation of MC3T3-E1 cells, as evidenced by decreased expression of Runx2 and Osterix along with reduced ALP activity. Mechanistically, HuR stabilized LRP6 mRNA and promoted its translation by binding to the 3'UTR of LRP6 mRNA, leading to activation of the downstream Wnt pathway. By this mechanism, osteoblastic differentiation of MC3T3-E1 cells was induced. In ovariectomized mice, overexpression of HuR alleviated osteoporosis-related phenotypes.

Conclusion

Overall, these data together support the promoting role of HuR in the osteoblastic differentiation, highlighting a potential novel strategy for osteoporosis treatment.
A systematic review and meta-analysis comparing complications following total hip arthroplasty for systemic lupus erythematosus versus for non-systemic lupus erythematosus
Authors: Huang Yiwei , Guan Danni , Li Yijin , Li Jiahao , Zeng Yirong
Published: April 2022

Background

Osteonecrosis of the femoral head is one of the most severe complications in systemic lupus erythematosus (SLE) patients. Total hip arthroplasty (THA) is an effective treatment for femoral head necrosis. However, there is no consensus on the specific effect of THA on SLE patients. The objective of the present study was to review the current evidence regarding rates of THA complications and postoperative function in systemic lupus erythematosus.

Methods

Two independent reviewers searched PubMed, Cochrane Library, and EMBASE from January 1, 2000, to December 29, 2021. The primary outcomes were postoperative complications, including deep vein thrombosis (DVT), hematoma, wound infection, dislocation, periprosthetic fracture, revision, mortality.

Results

A total of 179 articles yielded 28 studies eligible for inclusion with 10 studies used for meta-analysis. This study found a statistically significant difference in DVT, dislocation, wound infection, periprosthetic fracture, and revision.

Conclusions

This meta-analysis shows that SLE patients with THA are at an increased risk of DVT, wound infection, dislocation, periprosthetic fracture, revision, periprosthetic joint infection, following THA in comparison with non-SLE patients with THA. There was no adequate evidence to support the notion that the risk of seroma or hematoma following THA is increased in SLE. Also, there was no significant difference in HHS scores between SLE patients and non-SLE patients after THA.
Antepartum acute Stanford type A aortic dissection: a case report and literature review
Authors: Song Shibo , Lu Lin , Li Lihua , Peng Hua , Wu Xijie
Published: April 2022

Background

Aortic dissection in pregnancy is a life-threatening event that is associated with high maternal and foetal mortality. Most cases occur during the third trimester of pregnancy, Herein, we describe a case of a pregnant woman with acute type A aortic dissection at 28 weeks of gestation.

Case presentation

A previously healthy, 24-year-old gravida 2 para 1 woman was brought to the emergency department during at the 28 weeks of gestation and diagnosed with acute type A aortic dissection. Cesarean section was performed with the cardiac surgical team on standby for cardiopulmonary bypass and the patient delivered a baby weighing 1000 g. After the operation, we performed the Beatall procedure and total arch replacement with FET using the deep hypothermic circulatory arrest technique. Both the mother and child survived and recovered well. A review of the literature on antepartum acute aortic dissection during pregnancy is also presented.

Conclusion

Women should have a comprehensive, systematic physical examination before getting pregnant. Women at high risks of aortic dissection must undergo multidisciplinary evaluation and be counseled before pregnancy, once they become pregnant, their consistent aortic root diameter should be consistently monitored, and their blood pressure strictly controlled.
Consequences of rare diagnoses for education and daily life: development of an observation instrument
Authors: Jaeger Gunilla , Röjvik AnnCatrin , Hjelmquist Erland , Hansla André , Falkman Kerstin W.
Published: April 2022

Background

Ågrenska, a Swedish national centre for rare diagnoses and health conditions, has arranged courses for families of children with rare diagnoses for over thirty years, and has experienced that the conditions often have complex and varying consequences in the children´s everyday lives, not least in educational contexts. Knowledge of these consequences and of how to adapt the environment and educational methods is often lacking and the children´s educational needs are not met. Many professionals also report a lack of sources of knowledge. Knowledge formation and dissemination about educational consequences of rare diagnoses are thus of utmost importance. For this purpose, a broad observation instrument was constructed in order to gather knowledge on a group level concerning how functional impairments affect school and everyday situations, how consequences vary within each diagnosis and if there are diagnosis-specific features that lead to specific every day and pedagogical consequences.

Results

The instrument consists of 119 quantitative and 65 qualitative items and covers ten domains: social and communicative ability, emotions and behaviours, communication and language, ability to manage his/her disability and everyday life, activities of daily life, gross and fine motor skills, perception and worldview, prerequisites for learning and basic school abilities. The instrument is intended for use by educational professionals with knowledge of typical development and was content validated against existing instruments. The items were considered relevant as they, with few exceptions, appear in well-known assessment tools. Interrater reliability was based on the observations of six children. Each child was observed by two educators. Interrater reliability was calculated for the quantitative items and items with fixed response options, including yes/no answers, a total of 100 items, which are usually observed during the course. Interrater reliability reached 91%. Factor analysis and Cronbach´s alpha indicated good statistical properties and a multinomial regression gave reasonable results.

Conclusions

The instrument can be used to gather knowledge on a group level of educational and everyday consequences of rare diagnoses. This knowledge can be used to adapt methods and environment to meet the educational needs and create conditions for optimal learning and participation for children with rare health conditions.