bluuebunny/crossref_metadata_2025 huggingface dataset:
Flap-making patterns and corneal characteristics influence opaque bubble layer occurrence in femtosecond laser-assisted laser in situ keratomileusis
Authors: He Xi , Li Shi-Ming , Zhai Changbin , Zhang Li , Wang Yue , Song Xiumei , Wang Yi
Published: July 2022

Background

Opaque bubble layer (OBL), which generates from photo-disruptive procedures on the cornea, has been a common phenomenon during femtosecond laser-assisted refractive surgeries and it would potentially impact eye tracking and flap lifting. And we have observed that an updated flap-making pattern could form less OBL clinically than the traditional pattern, which needed further approval. Thus, the purpose of this study is to prove our observation and investigate the possible risk factors related to the occurrence and type of OBL in laser in situ keratomileusis (LASIK) flaps using the Visumax laser system.

Methods

This prospective study included 167 eyes of 86 patients (mean age: 27.5 ± 6.1 years) undergoing bilateral femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for myopia/myopic astigmatism by the same surgeon from April 2020 to August 2020. Preoperative data on refraction, central corneal thickness (CCT), and keratometry as well as intraoperative data were included for analysis. A new flap-making pattern creating an offset between flap-cut and side-cut was adopted to compare with the traditional pattern. The operation video of flap formation was analyzed to identify the existence and type of OBL. The area covered by OBL and the ratio of OBL to flap were calculated using Image J software.

Results

Among 167 eyes, 54 eyes (32.3%) developed OBLs, consisting of 31 as hard OBL coexisting with soft OBL, and 23 as soft OBL alone. The OBL incidence was significantly reduced in eyes with the new flap-making pattern compared with the traditional pattern (13.8% vs. 52.5%, P < 0.001). Hard OBLs had larger area ratios than soft OBLs (14.3 ± 8.3% vs. 1.1 ± 1.8%, P < 0.001). Univariate analyses revealed that eyes with more myopia, thicker CCT, and traditional flap-making patterns were more likely to develop OBLs. Multivariate analysis further confirmed that more myopia, thicker CCT, and traditional flap-making pattern were risk factors for OBLs. A Larger corneal diameter was associated with a higher incidence of hard OBL when applying the traditional flap-making process.

Conclusion

More myopia, thicker CCT, and larger corneal diameter were risk factors for OBL development during flap creation, whereas a flap-making pattern with an offset between flap-cut and side-cut could reduce the incidence of OBL.
Parent-focused online intervention to promote parents’ physical literacy and support children’s physical activity: results from a quasi-experimental trial
Authors: Ha Amy S. , He Qing , Lubans David R. , Chan Cecilia H. , Ng Johan Y. Y.
Published: July 2022

Background

The development of physical literacy (PL) early in life may influence children's subsequent physical activity (PA) participation and consequent health benefits across the life course. Interventions designed for parents are lacking, but such efforts can potentially enhance the PL of parents and their children’s PA participation. Additionally, there is insufficient evidence to support the feasibility of delivering a PL intervention using an online format. Therefore, the purpose of this study was to examine the feasibility and effectiveness of a parent-focused, theory-driven, online-delivered intervention designed to improve the parents’ PL and children’s PA behaviors.

Methods

A non-randomized trial was conducted to evaluate the effects of the program. 224 Hong Kong families (primary school-aged children and their parents) registered to the program were considered the experimental group and were exposed to an online intervention over three months. Another 220 families in Hong Kong were considered the comparison group and did not receive any intervention. Outcome measures included PA behaviors (daily steps and moderate-to-vigorous PA), parent–child co-activity behaviors, family PA routines, and parent perceived PL. Linear mixed models were used to analyze the differences in terms of changes in measured outcomes between groups over time.

Results

No significant group-by-time effects were found for children’s or parents’ PA behaviors. In terms of the family Co-PA routines, a small positive effect size in favor of the experimental group was found (p = .44, d = 0.2). Group-by-time effects favorable to the experimental group was detected for parent–child co-activity (p < .001, d = 0.7) and parental PL (p < .001, d = 0.9) at post-intervention. The results demonstrated that the intervention was acceptable and that there was potential for scale up.

Conclusions

Findings indicated that the intervention was effective in increasing parent–child co-activity and parent perceived PL. During the pandemic, online intervention delivery was found to be feasible. Using this mode of delivery, the intervention has the potential to reach a wide population in the local context.

Trial registration

The study was prospectively registered at the Chinese Clinical Trial Registry, Registration number: ChiCTR2100041903, Registered 09 January 2021.
Hip arthroscopy after periacetabular osteotomy for acetabular dysplasia – incidence and clinical outcome
Authors: Laboudie Pierre , Dymond Thomas , Kreviazuk Cheryl , Grammatopoulos George , Beaulé Paul E.
Published: July 2022

Background

The periacetabular osteotomy (PAO) is the treatment of choice for acetabular dysplasia and has demonstrated improvement in patient reported outcomes measures (PROMs) as well as acceptable long-term survival. However, acetabular dysplasia is also associated with intra-articular lesions that can negatively impact clinical outcome. This study aimed to analyse the incidence, operative findings, and outcomes of hip arthroscopy after PAO.

Methods

This is a single center retrospective study by querying our hip preservation prospectively collected database from 2006 to 2020. All patients having undergone hip arthroscopy after a PAO, with a minimal follow-up of one year, were identified. 202 PAOs were done with a mean age of 28.3 years (12.7 – 53.6) including 39 males and 167 females. Failure was defined as conversion to hip replacement. Demographics, surgical findings, reoperations, and PROMs (pre and post operatively at the last follow-up point only for hips not converted to hip replacement).

Results

Fifteen hips in 15 patients (7.4%) out of 202 PAOs underwent a hip arthroscopy at a mean time of 3.9 years (0.3–10.3) after PAO. There were 2 males, 13 females and the mean age was 29.8 years (18.5–45). 12 hips had no radiological osteoarthritis (Tönnis 0) and 3 hips had early osteoarthritis (Tönnis 1). At time of arthroscopy, all hips had a labral tear, 9 had a chondral damage ≥ Beck 4. Eight hips had labral debridement, 7 had labral repair, 2 had resection of adhesions and 4 underwent a femoral osteochondroplasty. Four hips (27%) were converted to a hip replacement at a mean time of 1.8 years(0.5–3.2) after hip arthroscopy. Patients converted to hip replacement were significantly older (p = 0.01), had a lower post-PAO LCEA (p = 0.01) and a higher post-PAO Tönnis angle (p = 0.02). There were no significant improvements in PROMs.

Conclusion

This study reports a hip arthroscopy reoperation rate after PAO of 7.4%. All three types of dysplasia (uncovered anteriorly, posteriorly, or globally) were present in this cohort. Twenty seven percent of patients were converted to hip replacement and PROMs were not significantly improved by hip arthroscopy. Therefore, this procedure should be approached with some caution.
Supervised physical therapy versus surgery for patients with lumbar spinal stenosis: a propensity score-matched analysis
Authors: Minetama Masakazu , Kawakami Mamoru , Teraguchi Masatoshi , Enyo Yoshio , Nakagawa Masafumi , Yamamoto Yoshio , Matsuo Sachika , Nakatani Tomohiro , Sakon Nana , Nakagawa Yukihiro
Published: July 2022

Background

Previous studies comparing surgical with nonsurgical treatment for lumbar spinal stenosis (LSS) reported that surgery is superior to nonsurgical treatments, but intensive and adequate volume of physical therapy were rarely performed. The purpose of this study was to compare the 1-year follow-up outcomes of patients with LSS treated with supervised physical therapy or surgery using propensity score-matched analysis.

Methods

A total of 224 patients with LSS who received supervised physical therapy (n = 38) or surgery (n = 186) were included, of which 66 were matched on baseline demographics, radiological findings, and patient-reported outcomes. The physical therapy group received supervised physical therapy twice weekly for 6 weeks. The physical therapy sessions included manual therapy, individually tailored exercises, cycling, and body-weight supported treadmill walking. The surgery group underwent decompression surgery with or without spinal fusion. A propensity score analysis was performed using a one-to-one nearest neighbor approach.

Results

The surgery group showed greater improvements in Zurich claudication questionnaire symptom severity and physical function, SF-36 physical functioning, bodily pain, and mental health, but had more severe stenosis and symptoms and mental health problems than the physical therapy group at baseline (P <  0.05). After propensity score matching, there were no significant differences in baseline characteristics, and all clinical outcomes at 1 year, except for a higher percentage of responders achieving minimum clinically important difference in the role-emotional subscale of SF-36 in the surgery group (P <  0.05).

Conclusions

When baseline characteristics were considered, supervised physical therapy yielded similar effects to lumbar surgery. These results suggest that supervised physical therapy is preferred over surgery as first-choice treatment, to prevent complications and to minimize health care costs, especially in mild to moderate cases of LSS.
Restructuring education activities for full online learning: findings from a qualitative study with Malaysian nursing students during Covid-19 pandemic
Authors: Romli Muhammad Hibatullah , Foong Chan Choong , Hong Wei-Han , Subramaniam Paramesevary , Wan Yunus Farahiyah
Published: July 2022

The COVID-19 pandemic and Movement Control Order have restricted learning activities from traditional face-to-face classrooms attendance shifted to full online learning in the student’s environment. The present study is aimed to explore pertaining issues on full online learning among nursing students and offer a contingency solution. Nursing students from one Malaysian public institution were recruited. The sessions were conducted online via teleconference and were recorded. The data were analysed using thematic analysis with the assistance of QDA Miner Lite software. Twenty-one students participated, resulting in four focus group discussions and three in-depth interviews. Three themes with a total of ten sub-themes were generated: (i) Full online learning has ramifications on life (it is about life; blurred division on education life and personal life; non-conducive environment for learning; health and well-being; human is an adaptable being while the transition takes time), (ii) full online learning is a medium of teaching and learning delivery but with several concerns (the boon and bane of fully online learning; challenges associated with full online learning; coping strategy in handling full online learning), and (iii) Foundation in teaching and learning is the key (role of the educator; teaching and learning approaches; motivation and regulation). A model of practice for full online learning was developed, consisting of some modifications to create a conducive and healthy learning environment. This study embarks on a more structured and standard online learning practice for making the Internet of Things and Industrial Revolution 4.0 concept a contemporary and mainstream education practice.
Ambivalence toward euthanasia and physician-assisted suicide has decreased among physicians in Finland
Authors: Piili Reetta P. , Louhiala Pekka , Vänskä Jukka , Lehto Juho T.
Published: July 2022

Background

Debates around euthanasia and physician-assisted suicide (PAS) are ongoing around the globe. Public support has been mounting in Western countries, while some decline has been observed in the USA and Eastern Europe. Physicians’ support for euthanasia and PAS has been lower than that of the general public, but a trend toward higher acceptance among physicians has been seen in recent years. The aim of this study was to examine the current attitudes of Finnish physicians toward euthanasia and PAS and whether there have been changes in these attitudes over three decades.

Methods

A questionnaire survey was conducted with all Finnish physicians of working age in 2020 and the results were compared to previous studies conducted in 1993, 2003 and 2013.

Results

The proportions of physicians fully agreeing and fully disagreeing with the legalization of euthanasia increased from 1993 to 2020 (from 5 to 25%, p < 0.001, and from 30 to 34%, p < 0.001, respectively). The number of physicians, who expressed no opinion for or against euthanasia (cannot say) decreased from 19 to 5% (p < 0.001) during the same period. The proportion of physicians having no opinion (cannot say) of whether a physician should be punished for assisting in a suicide decreased from 20 to 10% (p < 0.001).

Conclusions

This study shows that Finnish physicians’ ambivalence toward euthanasia and PAS has decreased. The ongoing debate has probably forced physicians to form more solid opinions on these matters. Our study highlights that attitudes toward euthanasia and PAS are still divided within the medical profession.
The impact of educational concerns and satisfaction on baccalaureate nursing students’ distress and quality of life during the Covid-19 pandemic; a cross-sectional study
Authors: Flølo Tone Nygaard , Gjeilo Kari Hanne , Andersen John Roger , Haraldstad Kristin , Hjelmeland Inger Helene Hardeland , Iversen Marjolein Memelink , Løyland Borghild , Norekvål Tone Merete , Riiser Kirsti , Rohde Gudrun , Urstad Kristin Hjortland , Utne Inger , Beisland Elisabeth Grov ,   on behalf of the LIVSFORSK network, Flølo Tone Nygaard , Gjeilo Kari Hanne , Andersen John Roger , Haraldstad Kristin , Hjelmeland Inger Helene Hardeland , Iversen Marjolein Memelink , Løyland Borghild , Norekvål Tone Merete , Riiser Kirsti , Rohde Gudrun , Urstad Kristin Hjortland , Utne Inger , Beisland Elisabeth Grov
Published: July 2022

Background

High levels of psychological distress and poor overall quality of life (QOL) have been identified among nursing students during the COVID-19 pandemic. The pandemic necessitated improvised reconstructions of educational curriculums and restrictions in clinical placement and training at campuses, possibly reducing educational quality.

Objectives

We explored whether baccalaureate nursing students’ concerns and satisfaction with the educational curriculum, focusing on the conduct of clinical training, were associated with perceived psychological distress and overall QOL.

Methods

Baccalaureate nursing students (N=6088) from five Norwegian universities were invited to an internet-based, cross-sectional survey during the second wave of the pandemic. The survey included COVID-19 specific questions on health, education and clinical training, the Fear of COVID-19 scale (FCV-19S), The Hopkins Symptom Checklist (SCL-5) and overall QOL. Data from national surveys on satisfaction with the educational curriculum, before and during the pandemic were used for comparison.

Results

In total, 2605 (43%) students responded, of whom 1591 (61%) had been engaged in clinical training during the pandemic. Overall, 53% were either satisfied or fully satisfied with their educational curriculum, with the level of satisfaction being significantly lower than pre-pandemic reference values. Also, 79% were concerned or highly concerned about the educational quality. In multiple regression analyses for all students, lower levels of satisfaction and higher levels of quality concerns were associated with worse SCL-5 scores. Furthermore, satisfaction with the educational curriculum was positively associated with overall QOL. For students engaged in clinical training, onlyconcerns about infecting otherswere additionally associated with psychological distress. None of the items related to clinical training were associated with overall QOL.

Conclusion

Nursing students’ educational satisfaction and quality concerns may significantly impact perceived psychological distress and overall QOL during a pandemic. However, with necessary adaptations implemented, concerns regarding the conduct of clinical training account for little of these associations.
The disease burden of migraine patients receiving prophylactic treatments in Korea: a population-based claims database analysis
Authors: Park Seonyoung , Han Sola , Suh Hae Sun
Published: July 2022

Background

Despite guideline recommendations, the limited benefits and failure of prophylactic treatment in patients with migraine have been reported. This study aimed to estimate the incremental burden (i.e., healthcare resource use and cost) of disease in patients who received at least one prophylactic treatment compared to those who did not.

Methods

This study analyzed the Health Insurance Review and Assessment Service database, which covers the entire population of Korea from December 2014 to November 2019. We included adult patients with migraine (≥18 years) who had ≥1 claim with migraine diagnosis (G43) or received ≥1 prescription of triptan or ergotamine between December 2015 and November 2018. We defined two groups: (1) migraine patients who received at least one prophylactic treatment (prophylaxis group) and (2) migraine patients who never received prophylactic treatments (non-prophylaxis group). We performed propensity score matching to balance the baseline covariates between the two groups. In a matched cohort, we estimated healthcare resource use and costs in terms of outpatient visits, outpatient visits to neurologists, emergency department (ED) visits, and hospitalizations.

Results

After matching, 633,709 and 633,709 patients were identified in the prophylaxis and non-prophylaxis groups, respectively. The healthcare resource utilization was significantly higher in the prophylaxis group than in the non-prophylaxis group in terms of the number of outpatient visits (2.34 vs 1.70), outpatient visits to neurologists (2.23 vs 1.61), ED visits (1.07 vs 1.05), and hospitalizations (1.12 vs 1.09) (all P <  0.05). The estimated annual costs per patient were significantly higher in the prophylaxis group than in the non-prophylaxis group for outpatient (102.37 USD vs. 62.46 USD), neurology outpatient (141.80 USD vs. 120.30 USD), and ED visits (550.51 USD vs. 234.14 USD) and hospitalization (817.01 USD vs. 645.97 USD) (all P <  0.001).

Conclusions

Migraine patients who received ≥1 prophylactic treatment had a higher burden of disease than migraine patients who received no prophylaxis. This indicates that despite migraine prophylaxis, the migraine-related disease burden remains high, and more efficient migraine prophylaxis strategies are needed.
The value measurement of emerging therapeutics in renal cell carcinoma: ASCO value framework and ESMO-MCBS
Authors: Ha Hyerim , Kang Jin Hyoung , Kim Do Yeun , Bae Seung Jin , Lee Hee Yeon
Published: July 2022

Purpose

Rapid development of novel therapeutics in renal cell carcinoma (RCC) has led to financial burden for patients and society. Value including clinical benefit, toxicity affecting quality of life and cost-effectiveness are a concern, prompting the need for tools to facilitate value assessment of therapeutics. This study reviews the value assessment tools, and evaluates the value of emerging therapeutics in RCC.

Materials and methods

Two medical oncologists used American Society of Clinical Oncology value framework (ASCO VF) v2.0 and European Society for Medical Oncology-magnitude of clinical benefit scale (ESMO-MCBS) v1.1 to phase 3 trials evaluating first-line therapy in patients with metastatic RCC. Follow-up (FU) reports and extended survival data were included. Equivocal aspects and limitations of the tools were discussed.

Results

Six trials (COMPARZ, CheckMate 214, JAVELIN renal 101, Keynote 426, CLEAR, and CheckMate 9ER) were assessed. The control arm was standard-of-care sunitinib in all trials. ASCO VF’s net health benefit, calculated as clinical benefit, toxicity and other bonus point was 11 in pazopanib, 41.9 in nivolumab plus ipilimumab, 22.4 in axitinib plus avelumab, 48.7 in axitinib plus pembrolizumab, 35.2 in lenvatinib plus pembrolizumab, and 50.8 in cabozantinib plus nivolumab. A higher score means a greater treatment benefit. ESMO-MCBS gave grade 5 to nivolumab plus ipilimumab, 4 to pazopanib, lenvatinib plus pembrolizumab and cabozantinib plus nivolumab, 3 to axitinib plus avelumab or pembrolizumab. Both tools had unclear aspects to be applied to clinical practice, and should be more clearly defined, such as endpoint for determining survival benefits or how to standardize quality of life and toxicity.

Conclusions

ASCO VF and ESMO-MCBS were applied to evaluate the newly emerging drugs in RCC and assessed their value. In-depth discussion by experts in various fields is required for appropriate clinical application in a real-world setting.
Preparedness and management during the first phase of the COVID-19 outbreak - a survey among emergency primary care services in Norway
Authors: Dale Jonas Nordvik , Morken Tone , Eliassen Knut Eirik , Blinkenberg Jesper , Rørtveit Guri , Hunskaar Steinar , Rebnord Ingrid Keilegavlen , Baste Valborg
Published: July 2022

Background

The emergency primary care (EPC) services in Norway have been at the frontline of the COVID-19 pandemic. Knowledge about the EPC services’ management of the COVID-19 outbreak can be used to prepare for future outbreaks and improve patient management. The objectives of this study were to identify pandemic preparedness and management strategies in EPC centres in Norway during the COVID-19 outbreak.

Methods

Questions regarding patient management of the COVID-19 outbreak were included in data collection for the National Out-Of-Hours Services Registry. The data collection was web-based, and an invitation was sent by email to the managers of all EPC services in Norway in June 2020. The EPC services were asked questions about pre-pandemic preparedness, access to personal protective equipment (PPE), organizational measures taken, and how staffing was organized during the onset of the pandemic.

Results

There were 169 municipal and inter-municipal EPC services in Norway in 2020, and all responded to the questionnaire. Among the EPC services, 66.7% (n = 112) had a pandemic plan, but only 4.2% had performed training for pandemic preparedness. Further, fewer than half of the EPC centres (47.5%) had access to supplies of PPE, and 92.8% answered that they needed extra supplies of PPE. 75.3% of the EPC services established one or more respiratory clinics. Staffing with other personnel than usual was done in 44.6% (n = 74) of the EPC services. All EPC services except one implemented new strategies for assessing patients, while about half of the wards implemented new strategies for responding to emergency calls.

None of the largest EPC services experienced that their pandemic plan was adequate, while 13.3% of the medium-sized EPC services and 48.9% of the small EPC services reported having an adequate pandemic plan.

Conclusions

Even though the EPC services lacked well-tested plans and had insufficient supplies of PPE at the outbreak of the COVID-19 pandemic, most services adapted to the pandemic by altering the ways they worked and by hiring health care professionals from other disciplines. These observations may help decision makers plan for future pandemics.
“To enroll or not to enroll”: a qualitative study on preferences for dental insurance in Iran
Authors: Vahidi Jamileh , Takian Amirhossein , Amini-Rarani Mostafa , Moeeni Maryam
Published: July 2022

Background

Oral public health services are included in primary healthcare. Although oral diseases are preventable, improving oral health has become a concern in many countries. Evidence shows that functioning insurance coverage can significantly increase the use of dental health services, improve quality of services, and reduce financial barriers to utilization. Little evidence exists on households’ preferences for dental insurance in Iran. This study seeks to identify the households’ preferences for dental insurance in Tehran-Iran.

Method

This is a qualitative study. We interviewed 84 participants who visited selected public and private dental clinics in Tehran-Iran, from October 2018 until January 2019. All interviews were recorded and transcribed verbatim. We used a mixed inductive/deductive approach for thematic analysis of the interviews.

Results

We identified two main themes and 12 sub-themes: pecuniary attributes (insurance premium, coinsurance, insurance coverage granted, discounting option, reimbursement of expenses), and non-pecuniary attributes (notification status, ethical issues, benefits package, contract providers with health insurance, quality of service centers, administrative process, and dental insurance scheme).

Conclusion

Our participants considered both pecuniary and non-pecuniary attributes for choosing a dental insurance package. Our findings could help, we envisage, policymakers understand Iranian households’ preferences for a dental insurance scheme that they afford to buy.
Healthcare professionals feel empowered by implementing a hospital-based multifaceted intervention: a qualitative study using inductive thematic analysis
Authors: Klooster E. , Koenders N. , Vermeulen-Holsen J. , Vos L. , van der Wees P. J. , Hoogeboom T. J.
Published: July 2022

Background

Most patients are insufficiently physically active during their hospital stay, and this is associated with poor health and delayed recovery. Hospital-based multifaceted interventions aim to encourage patients to engage in physical activity. Ban Bedcentricity is one such intervention. Its value – and that of others similar to it – for healthcare professionals has not been studied yet. Whether an intervention looks and feels right, and whether it does the job well, is important for healthcare professionals and thus its use. Understanding value for healthcare professionals seems crucial for the long-term adoption and implementation of interventions. Therefore, we studied healthcare professionals’ perceptions of value in terms of the implementation of a multifaceted intervention that aimed at improving physically active behaviour in patients during their hospital stay.

Methods

Using Ban Bedcentricity as a case study to focus on healthcare professionals’ perceptions about multifaceted interventions, we conducted a qualitative study between November 2019 and September 2020. Semi-structured interviews were conducted with purposefully selected physicians, physiotherapists, and nurses (assistants) until theoretical data saturation was reached. Inductive thematic analysis was used to identify key themes and develop a conceptual model.

Results

We interviewed 15 healthcare professionals and formulated six key themes from these interviews. The participants said that Ban Bedcentricity empowered them in their beliefs about the importance of physical activity for hospitalized patients (theme 1). They also indicated that it made them more aware of the value of physical activity (theme 2) and skilled to promote physical activity as part of their professional role (theme 3). Similarly, they noted that it enabled them to shift from providing hands-on support to verbal coaching (theme 4). Other aspects that the participants valued were the increased possibilities for teamwork (theme 5) and the routinized physical activity promotion in usual care (theme 6). The challenges discussed by the participants were prioritizing activities that promoted physical activity, especially because of a high workload, and avoiding relapses of new routinized work practices related to physical activity promotion if insufficient long-term support and training were provided.

Conclusions

Our conceptual model shows that the implementation of a hospital-based multifaceted intervention by healthcare professionals empowers their beliefs, and improves their awareness, skills, professional roles, teamwork, and work routinization. These values are typically overlooked, despite potentially being important facilitators for long-term implementation.
Generational synaptic functions of GABAA receptor β3 subunit deteriorations in an animal model of social deficit
Authors: Chu Ming-Chia , Wu Han-Fang , Lee Chi-Wei , Chung Yueh-Jung , Chi Hsiang , Chen Po See , Lin Hui-Ching
Published: July 2022

Background

Disruption of normal brain development is implicated in numerous psychiatric disorders with neurodevelopmental origins, including autism spectrum disorder (ASD). Widespread abnormalities in brain structure and functions caused by dysregulations of neurodevelopmental processes has been recently shown to exert adverse effects across generations. An imbalance between excitatory/inhibitory (E/I) transmission is the putative hypothesis of ASD pathogenesis, supporting by the specific implications of inhibitory γ-aminobutyric acid (GABA)ergic system in autistic individuals and animal models of ASD. However, the contribution of GABAergic system in the neuropathophysiology across generations of ASD is still unknown. Here, we uncover profound alterations in the expression and function of GABAA receptors (GABAARs) in the amygdala across generations of the VPA-induced animal model of ASD.

Methods

The F2 generation was produced by mating an F1 VPA-induced male offspring with naïve females after a single injection of VPA on embryonic day (E12.5) in F0. Autism-like behaviors were assessed by animal behavior tests. Expression and functional properties of GABAARs and related proteins were examined by using western blotting and electrophysiological techniques.

Results

Social deficit, repetitive behavior, and emotional comorbidities were demonstrated across two generations of the VPA-induced offspring. Decreased synaptic GABAAR and gephyrin levels, and inhibitory transmission were found in the amygdala from two generations of the VPA-induced offspring with greater reductions in the F2 generation. Weaker association of gephyrin with GABAAR was shown in the F2 generation than the F1 generation. Moreover, dysregulated NMDA-induced enhancements of gephyrin and GABAAR at the synapse in the VPA-induced offspring was worsened in the F2 generation than the F1 generation. Elevated glutamatergic modifications were additionally shown across generations of the VPA-induced offspring without generation difference.

Conclusions

Taken together, these findings revealed the E/I synaptic abnormalities in the amygdala from two generations of the VPA-induced offspring with GABAergic deteriorations in the F2 generation, suggesting a potential therapeutic role of the GABAergic system to generational pathophysiology of ASD.
To spray or target mosquitoes another way: focused entomological intelligence guides the implementation of indoor residual spraying in southern Mozambique
Authors: Alafo Celso , Martí-Soler Helena , Máquina Mara , Malheia Arlindo , Aswat Ayesha S. , Koekemoer Lizette L. , Colborn James , Lobo Neil F. , Tatarsky Allison , Williams Yasmin A. , Marrenjo Dulcisária , Cuamba Nelson , Rabinovich Regina , Alonso Pedro , Aide Pedro , Saúte Francisco , Paaijmans Krijn P.
Published: July 2022

Background

To eliminate malaria in southern Mozambique, the National Malaria Control Programme and its partners are scaling up indoor residual spraying (IRS) activities in two provinces, Gaza and Inhambane. An entomological surveillance planning tool (ESPT) was used to answer the programmatic question of whether IRS would be effective in target geographies, given limited information on local vector bionomics.

Methods

Entomological intelligence was collected in six sentinel sites at the end of the rainy season (April–May 2018) and the beginning of the dry season (June–July 2018). The primary objective was to provide an ‘entomological snapshot’ by collecting question-based, timely and high-quality data within one single week in each location. Host-seeking behaviour (both indoors and outdoors) was monitored by human-baited tent traps. Indoor resting behaviour was quantified by pyrethrum spray catches and window exit traps.

Results

Five different species or species groups were identified: Anopheles funestus sensu lato (s.l.) (66.0%), Anopheles gambiae s.l. (14.0%), Anopheles pharoensis (1.4%), Anopheles tenebrosus (14.1%) and Anopheles ziemanni (4.5%). Anopheles funestus sensu stricto (s.s.) was the major vector among its sibling species, and 1.9% were positive for Plasmodium falciparum infections. Anopheles arabiensis was the most abundant vector species within the An. gambiae complex, but none tested positive for P. falciparum infections. Some An. tenebrosus were positive for P. falciparum (1.3%). When evaluating behaviours that impact IRS efficacy, i.e. endophily, the known primary vector An. funestus s.s., was found to rest indoors—demonstrating at least part of its population will be impacted by the intervention if insecticides are selected to which this vector is susceptible. However, other vector species, including An. gambiae s.l., An. tenebrosus, An. pharoensis and An. ziemanni, showed exophilic and exophagic behaviours in several of the districts surveilled.

Conclusion

The targeted approach to entomological surveillance was successful in collecting question-based entomological intelligence to inform decision-making about the use of IRS in specific districts. Endophilic An. funestus s.s. was documented as being the most prevalent and primary malaria vector suggesting that IRS can reduce malaria transmission, but the presence of other vector species both indoors and outdoors suggests that alternative vector control interventions that target these gaps in protection may increase the impact of vector control in southern Mozambique.
Managing the medical resources of a national insurance program: lessons based on China’s NCMS
Authors: Qian Wenqiang , Cheng Xiangyu
Published: July 2022

Background

The security of medical insurance fund is very important to health equity. In China, the expenditure of medical insurance fund has increased sharply year after year, and the balance of local medical insurance fund is difficult to sustain. To realize the equitable distribution of the medical insurance burden, the central government has to continuously increase transfer payments, which causes regional unfairness in the distribution of central financial resources. This paper explores the influence of central transfer payments on the balance of medical insurance fund, influential mechanisms, and the strategic behavior of local governments.

Methods

First, we constructed a dynamic game model between central government and local governments and analyzed the mechanism of central transfer payments affecting the balance of local medical insurance fund. Then, based on the provincial panel data of 28 provincial administrative regions in China from 2004 to 2014, an empirical test was made. The spatial regression model was constructed, and the transfer payments obtained by neighboring provinces in the previous year were taken as instrumental variables.

Results

Central transfer payments led to strategic behaviors by local governments that resulted in increased local health insurance fund expenditures and lower balance rates. Moreover, the central transfer payments demonstrated “path dependence”. Central transfer payments had a significant negative influence on the local NCMS fund balance rate. The local government subsidy and per capita GDP had a significant positive impact on the local NCMS fund balance rate. The obtained transfer payments of local governments had a significant space correlation. This study based on NCMS data remains valid.

Conclusions

Central transfer payments induced the strategic behavior of local governments, which neglected to supervise the expenditure of medical insurance fund, reducing the efficiency of medical insurance fund management and use. The financial resources of medical insurance fund are unevenly distributed among provinces. Measures such as strengthening the supervision ability and initiatives of local governments, refining the central transfer payment mechanism, promoting the economic growth of western regions, and increasing rates for individual contributions appropriately can ensure that the medical insurance fund are used well and distributed equitably.
Recent evidence from omic analysis for redox signalling and mitochondrial oxidative stress in COPD
Authors: Mumby Sharon , Adcock Ian M
Published: July 2022

COPD is driven by exogenous and endogenous oxidative stress derived from inhaled cigarette smoke, air pollution and reactive oxygen species from dysregulated mitochondria in activated inflammatory cells within the airway and lung. This is compounded by the loss in antioxidant defences including FOXO and NRF2 and other antioxidant transcription factors together with various key enzymes that attenuate oxidant effects. Oxidative stress enhances inflammation; airway remodelling including fibrosis and emphysema; post-translational protein modifications leading to autoantibody generation; DNA damage and cellular senescence. Recent studies using various omics technologies in the airways, lungs and blood of COPD patients has emphasised the importance of oxidative stress, particularly that derived from dysfunctional mitochondria in COPD and its role in immunity, inflammation, mucosal barrier function and infection. Therapeutic interventions targeting oxidative stress should overcome the deleterious pathologic effects of COPD if targeted to the lung. We require novel, more efficacious antioxidant COPD treatments among which mitochondria-targeted antioxidants and Nrf2 activators are promising.
Effects of portal vein resection and hepatic artery resection on long-term survival in Klatskin tumor: a meta-analysis
Authors: Song Yun , Zhang Yujie , Zhen Zhijie , Huang Zhaohui
Published: July 2022

Background

Surgical treatment is currently the only way to achieve the clinical cure for Klatskin tumor. However, whether combined vascular resection should be combined during surgeries is still controversial. The aim of this article was to analyze the effect of portal vein resection (PVR) and hepatic artery resection (HAR) on the long-term survival after surgery for Klatskin tumor.

Methods

Articles about Klatskin tumor with PVR and HAR, which were published from 2000 to 2020, were searched using PubMed, Embase, and EBSCO. HR with a 95% CI of overall survival, recurrence-free survival, disease-free survival, 3- and 5-year survival rate, and median survival time were reported to evaluate prognosis.

Results

A total of 17 articles were included. The total case number of these studies was 3150 (685 in the PVR group, 345 in the HAR group, and 2120 in the control group). Survival analyses showed that both vascular resection types were poor prognostic factors (PVR: HR = 1.50, 95% CI = 1.24–1.81, P < 0.001; HAR: HR = 1.68, 95% CI = 1.26–2.24, P < 0.001; the pooled effect size of the two groups: HR = 1.55, 95% CI = 1.32–1.82, P < 0.001). In general, the analyses of 3- and 5-year survival and median survival time showed that both vascular resection types tended to be poor prognostic factors, but most of recent researches showed that the PVR did not lead to a poor prognosis.

Conclusion

PVR should be used when necessary to achieve R0 resection of Klatskin tumor and improve the long-term survival of patients. Whether HAR should be performed or not is still need to be evaluated.
Emergency surgical consultation for cancer patients: identifying the prognostic determinants of health
Authors: Taqi Kadhim , Kim Diane , Yip Lily , Laane Charlotte , Rana Zeeshan , Hameed Morad , Hamilton Trevor , Stuart Heather
Published: July 2022

Background

Patients with malignancy often require urgent surgical consultation for treatment or palliation of disease. The objective of this study is to explore the prognostic determinants affecting care in acute cancer-related surgical presentations and the effect on patient outcomes.

Main body

This is a retrospective review of patients referred to the acute general surgery (ACS) service at a tertiary hospital for management of cancer-related problem from July 2017 to September 2018. Patient demographics, course in hospital, and survival were recorded. Multivariant logistic regression and Kaplan-Meier estimates were performed. One hundred eighty-nine patients were identified (53% female) with a mean age of 65.9 years. Forty-two patients (22%) were newly diagnosed with cancer on presentation, and 94 (50%) patients had metastatic disease. Cancer staging was completed in 84% of patients, and 65% had multidisciplinary team (MDT) assessment during their hospital stay. Surgery was performed on 90 (48%) patients, of which 31.2% was with palliative intent. Overall mortality was 56% with 30- and 60-day mortality of 15% and 22%, respectively. The adjusted odds ratio (OR) for a 60-day mortality was high in patients presenting with new cancer diagnosis (OR 3.18, 95% CI 1.18–9.02, p=0.03), metastatic disease (OR 5.11, 95% CI 2.03–12.85, p=0.001), or systemic therapy on presentation (OR 3.46, 95% CI 1.30–9.22, p=0.013).

Conclusion

Emergency surgical referral is common in patients with malignancy. Surgical decision making can be challenging due to the heterogeneity of this population and their associated comorbidities. Optimizing prognostic determinants such as goal-directed palliative care, MDT discussions, and bridging to systemic therapy can improve patient outcomes.
The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats
Authors: Yao Zhiqiu , Lin Maosen , Lin Tao , Gong Xinbao , Qin Pin , Li Hailing , Kang Tiezhu , Ye Jing , Zhu Yanyun , Hong Qiwen , Liu Ya , Li Yunsheng , Wang Juhua , Fang Fugui
Published: July 2022

Insulin-like growth factor-binding protein-5 (IGFBP-5) has recently been shown to alter the reproductive capacity by regulating insulin-like growth factor (IGF) bioavailability or IGF-independent effects. The present study aimed to investigate the effect and mechanism of IGFBP-5 on the onset of puberty in female rats. Immunofluorescence and real-time quantitative PCR were used to determine the expression and location of IGFBP-5 mRNA and protein distribution in the infant's hypothalamus-pituitary-ovary (HPO) axis prepuberty, peripuberty, puberty and adult female rats. Prepubertal rats with IGFBP-5 intracerebroventricular (ICV) were injected to determine the puberty-related genes expression and the concentrations of reproductive hormones. Primary hypothalamic cells were treated with IGFBP-5 to determine the expression of puberty-related genes and the Akt and mTOR proteins. Results showed that Igfbp-5 mRNA and protein were present on the HPO axis. The addition of IGFBP-5 to primary hypothalamic cells inhibited the expression of Gnrh and Igf-1 mRNAs (P < 0.05) and increased the expression of AKT and mTOR protein (P < 0.01). IGFBP-5 ICV-injection delayed the onset of puberty, reduced Gnrh, Igf-1, and Fshβ mRNAs, and decreased the concentrations of E2, P4, FSH,serum LH levels and the ovaries weight (P < 0.05). More corpus luteum and fewer primary follicles were found after IGFBP-5 injection (P < 0.05).
MicroRNA-22-3p ameliorates Alzheimer’s disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus
Authors: Xia Pengcheng , Chen Jing , Liu Yingchao , Cui Xiaolin , Wang Cuicui , Zong Shuai , Wang Le , Lu Zhiming
Published: July 2022

Background

Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer’s disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated.

Methods

The ameliorating effect of miR-22-3p on apoptosis of the Aβ-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis.

Results

The miR-22-3p played an important role in ameliorating apoptosis in the Aβ-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aβ deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments.

Conclusion

Our study showed that miR-22-3p could improve apoptosis and reduce Aβ deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.
A subset of gut leukocytes has telomerase-dependent “hyper-long” telomeres and require telomerase for function in zebrafish
Authors: Ellis Pam S. , Martins Raquel R. , Thompson Emily J. , Farhat Asma , Renshaw Stephen A. , Henriques Catarina M.
Published: July 2022

Background

Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. T and B-cells cells are somatic cells that can break this rule and can modulate telomerase expression in a homeostatic manner. Whereas it seems intuitive that an immune cell type that depends on regular proliferation outbursts for function may have evolved to modulate telomerase expression it is less obvious why others may also do so, as has been suggested for macrophages and neutrophils in some chronic inflammation disease settings. The gut has been highlighted as a key modulator of systemic ageing and is a key tissue where inflammation must be carefully controlled to prevent dysfunction. How telomerase may play a role in innate immune subtypes in the context of natural ageing in the gut, however, remains to be determined.

Results

Using the zebrafish model, we show that subsets of gut immune cells have telomerase-dependent”hyper-long” telomeres, which we identified as being predominantly macrophages and dendritics (mpeg1.1+ and cd45+mhcII+). Notably, mpeg1.1+ macrophages have much longer telomeres in the gut than in their haematopoietic tissue of origin, suggesting that there is modulation of telomerase in these cells, in the gut. Moreover, we show that a subset of gut mpeg1.1+ cells express telomerase (tert) in young WT zebrafish, but that the relative proportion of these cells decreases with ageing. Importantly, this is accompanied by telomere shortening and DNA damage responses with ageing and a telomerase-dependent decrease in expression of autophagy and immune activation markers. Finally, these telomerase-dependent molecular alterations are accompanied by impaired phagocytosis of E. coli and increased gut permeability in vivo.

Conclusions

Our data show that limiting levels of telomerase lead to alterations in gut immunity, impacting on the ability to clear pathogens in vivo. These are accompanied by increased gut permeability, which, together, are likely contributors to local and systemic tissue degeneration and increased susceptibility to infection with ageing.

Graphical Abstract