bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study
Authors: Filiatreau Lindsey M. , Edwards Jessie K. , Masilela Nkosinathi , Gómez-Olivé F. Xavier , Haberland Nicole , Pence Brian W. , Maselko Joanna , Muessig Kathryn E. , Kabudula Chodziwadziwa Whiteson , Dufour Mi-Suk Kang , Lippman Sheri A. , Kahn Kathleen , Pettifor Audrey
Published: September 2023

Introduction

Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era.

Methods

Using medical record data, we conducted a retrospective cohort study among youth aged 18–24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences.

Results

A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression.

Conclusions

Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV— however, meeting UNAIDS’ 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.
Characterizing the impacts of public health control measures on domestic violence services: qualitative interviews with domestic violence coalition leaders
Authors: Horney Jennifer A. , Fleury-Steiner Ruth , Camphausen Lauren C. , Wells Sarah A. , Miller Susan L.
Published: September 2023

Background

Prior to the availability of pharmaceutical control measures, non-pharmaceutical control measures, including travel restrictions, physical distancing, isolation and quarantine, closure of schools and workplaces, and the use of personal protective equipment were the only tools available to public health authorities to control the spread of COVID-19. The implementation of these non-pharmaceutical control measures had unintended impacts on the ability of state and territorial domestic violence coalitions to provide services to victims.

Methods

A semi-structured interview guide to assess how the COVID-19 pandemic impacted service provision and advocacy generally, and how COVID-19 control measures specifically, created barriers to services and advocacy, was developed, pilot tested, and revised based on feedback. Interviews with state and territorial domestic violence coalition executive directors were conducted between November 2021 and March 2022. Transcripts were inductively and deductively coded using both hand-coding and qualitative software.

Results

Forty-five percent (25 of 56) of state and territorial domestic violence coalition executive directors representing all 8 National Network to End Domestic Violence (NNEDV) regions were interviewed. Five themes related to the use of non-pharmaceutical pandemic control measures with impacts on the provision of services and advocacy were identified.

Conclusions

The use of non-pharmaceutical control measures early in the COVID-19 pandemic had negative impacts on the health and safety of some vulnerable groups, including domestic violence victims. Organizations that provide services and advocacy to victims faced many unique challenges in carrying out their missions while adhering to required public health control measures. Policy and preparedness plan changes are needed to prevent unintended consequences of control measure implementation among vulnerable groups as well as to identify lessons learned that should be applied in future disasters and emergencies.
Foot characteristics of the daily-life gait in postmenopausal females with distal radius fractures: a cross-sectional study
Authors: Yamamoto Akiko , Fujita Koji , Yamada Eriku , Ibara Takuya , Nihey Fumiyuki , Inai Takuma , Tsukamoto Kazuya , Kobayashi Yoshiyuki , Nakahara Kentaro , Okawa Atsushi
Published: September 2023

Background

Gait decline in older adults is related to falling risk, some of which contribute to injurious falls requiring medical attention or restriction of activity of daily living. Among injurious falls, distal radius fracture (DRF) is a common initial fragility fracture associated with the subsequent fracture risk in postmenopausal females. The recent invention of an inertial measurement unit (IMU) facilitates the assessment of free-living gait; however, little is known about the daily gait characteristics related to the risk of subsequent fractures. We hypothesized that females with DRF might have early changes in foot kinematics in daily gait. The aim of this study was to evaluate the daily-life gait characteristics related to the risk of falls and fracture.

Methods

In this cross-sectional study, we recruited 27 postmenopausal females with DRF as their first fragility fracture and 28 age-matched females without a history of fragility fractures. The participants underwent daily gait assessments for several weeks using in-shoe IMU sensors. Eight gait parameters and each coefficient of variance were calculated. Some physical tests, such as hand grip strength and Timed Up and Go tests, were performed to check the baseline functional ability.

Results

The fracture group showed lower foot angles of dorsiflexion and plantarflexion in the swing phase. The receiver operating characteristic curve analyses revealed that a total foot movement angle (TFMA) < 99.0 degrees was the risk of subsequent fracture.

Conclusions

We extracted the daily-life gait characteristics of patients with DRF using in-shoe IMU sensors. A lower foot angle in the swing phase, TFMA, may be associated with the risk of subsequent fractures, which may be effective in evaluating future fracture risk. Further studies to predict and prevent subsequent fractures from daily-life gait are warranted.
The effect of low-frequency high-intensity ultrasound combined with aspirin on tooth movement in rats
Authors: Xin Jiao , Zhan Xinxin , Zheng Fu , Li Huazhi , Wang Yixiang , Li Cuiying , Jiang Jiuhui
Published: September 2023

Background

Given the difficulties or incapacity of teeth movement in orthodontic treatment, the ways to speed tooth movement must be investigated. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) were utilized to treat pain caused by tooth movement during orthodontic treatment. The purpose of this study is to examine the impact of aspirin and low-frequency high-intensity ultrasound (LFHIU) on rat orthodontic tooth movement in rats.

Methods

Thirty-six male Sprague-Dawley rats were divided into three groups: orthodontic (O), ultrasound-treated orthodontic (OU), and ultrasound-treated orthodontic with aspirin gavage (OUA) group. In the OU and OUA group, LFHIU (44 W/cm2, 28 kHz) was applied to the buccal side of the maxillary first molar alveolar bone for 10 s every day. In the OUA group, aspirin was given by gavage every day. The rats were sacrificed on days 1, 3, 7, and 14.

Results

After ultrasonic treatment, the speed of tooth movement was increased by about 1.5 times. And the number of osteoclasts considerably increased by about 2 times. However, they decreased slightly after aspirin gavage. By Applying ultrasound therapy, Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) levels in periodontal tissue were elevated. Aspirin was able to reduce these increases. Results from Micro Computed Tomography (Micro-CT) revealed that bone mineral density decreased by about 1/5 after ultrasound treatment on the compression side. The rate of bone mineral apposition indicated that bone was forming under tension, and that of the OU group increased by about 1.3 times that O group.

Conclusions

Although aspirin slowed this trend, LFHIU still enhanced overall tooth mobility in orthodontic treatment.
Intra-oral scan segmentation using deep learning
Authors: Vinayahalingam Shankeeth , Kempers Steven , Schoep Julian , Hsu Tzu-Ming Harry , Moin David Anssari , van Ginneken Bram , Flügge Tabea , Hanisch Marcel , Xi Tong
Published: September 2023

Objective

Intra-oral scans and gypsum cast scans (OS) are widely used in orthodontics, prosthetics, implantology, and orthognathic surgery to plan patient-specific treatments, which require teeth segmentations with high accuracy and resolution. Manual teeth segmentation, the gold standard up until now, is time-consuming, tedious, and observer-dependent. This study aims to develop an automated teeth segmentation and labeling system using deep learning.

Material and methods

As a reference, 1750 OS were manually segmented and labeled. A deep-learning approach based on PointCNN and 3D U-net in combination with a rule-based heuristic algorithm and a combinatorial search algorithm was trained and validated on 1400 OS. Subsequently, the trained algorithm was applied to a test set consisting of 350 OS. The intersection over union (IoU), as a measure of accuracy, was calculated to quantify the degree of similarity between the annotated ground truth and the model predictions.

Results

The model achieved accurate teeth segmentations with a mean IoU score of 0.915. The FDI labels of the teeth were predicted with a mean accuracy of 0.894. The optical inspection showed excellent position agreements between the automatically and manually segmented teeth components. Minor flaws were mostly seen at the edges.

Conclusion

The proposed method forms a promising foundation for time-effective and observer-independent teeth segmentation and labeling on intra-oral scans.

Clinical significance

Deep learning may assist clinicians in virtual treatment planning in orthodontics, prosthetics, implantology, and orthognathic surgery. The impact of using such models in clinical practice should be explored.
Fracture resistance of monolithic translucent zirconia crown bonded with different self-adhesive resin cement: influence of MDP-containing zirconia primer after aging
Authors: Tyor Shaima , Al-Zordk Walid , Sakrana Amal Abdelsamad
Published: September 2023

Objectives

Successful ceramic restorations depend on the strong bonding with resin cement and even stress distribution. The aim of this study was to evaluate the impact of adding MDP-containing zirconia primer before self-adhesive resin cements with different functional acidic monomers on fracture resistance of monolithic zirconia crown.

Materials and methods

Eighty defect-free human maxillary premolars were divided according to the cement type and application of MDP-containing zirconia primer into eight groups (n = 10): Calibra Universal (C), Calibra Universal combined with zirconia primer (CZ), RelyX U200 (R), RelyXU200 combined with zirconia primer (RZ), Panavia SA Cement Plus (P), Panavia SA Cement Plus combined with zirconia primer (PZ), Multilink Speed (M), and Multilink Speed combined with zirconia primer (MZ). After teeth preparation and fabrication of zirconia crowns, each crown was bonded to its corresponding tooth. All specimens were subjected to 10,000 thermocycles between 5 and 55°C, followed by cyclic load (50 N) for 240,000 cycles. Each specimen was subjected to a static axial load until fracture using universal testing machine and the fracture load was recorded. The fracture mode studied and recorded. The fracture load results were analyzed using two-way ANOVA test (α = 0.05).

Results

A significant interaction (P = 0.038) of combining MDP-containing zirconia primer and cement type on fracture resistance of monolithic zirconia crown was detected. The mean fracture load values of zirconia crown were significantly influenced by the combined application of the MDP-containing zirconia primer with Calibra Universal (P = 0.01), RelyX U200 (P < 0.001), and Multilink Speed (P = 0.038), while there was no significant difference with Panavia SA Cement Plus (P = 0.660). There was significant difference (F = 20.69, P < 0.001) between the mean fracture loads of groups with self-adhesive cements (C, R, P, and M groups). The highest fracture load was recorded with RZ group (2446.90 ± 126.72 N) while the lowest fracture load was recorded with C group (1623.18 ± 149.86 N).

Conclusions

The self-adhesive resin cement with different acidic functional monomer affects the fracture resistance of monolithic zirconia crown. Application of MDP-containing primer could improve the fracture resistance of monolithic zirconia crown with most self-adhesive cements. The application of an MDP-containing primer had no impact on the fracture resistance of monolithic translucent zirconia crown bonded by MDP-containing self-adhesive resin cement.
Patients’ experiences of adverse symptoms, emotions, and coping strategies in connection to treatment of head and neck cancer - an interview study
Authors: Saghafi Ellie , Andås Charlotte Andrén , Bernson Jenny , Kjeller Göran
Published: September 2023

Purpose

This study aimed to increase the understanding of emotions and coping strategies used by head and neck cancer patients before cancer treatment, and to explore their emotions and coping strategies in relation to symptoms and side effects after treatment. Furthermore, we aimed to investigate the patients’ perceptions of received treatment and support.

Methods

Semi-structured in-depth interviews were conducted with 10 patients who had been treated for head and neck cancer, which included radiotherapy, at the Department of Oncology and the Department of Oral and Maxillofacial Surgery at Sahlgrenska University Hospital in Gothenburg. The interviews were analyzed in accordance with the method for Qualitative Content Analysis.

Results

The result picture revealed three head themes. The first theme “Management of simultaneously influencing mind-sets before cancer treatment” described the patients experiences of feeling “Scared and worried,” “Lonely and disappointed,” and “Relieved and confident”, and how they tried to handle the diagnosis and preparations for treatment by “Applying a positive mind-set”, “Searching for support,” and “Trusting the healthcare system”. The second theme “Experiences of becoming a pale shadow of oneself”, illustrated experiences of affecting post-treatment symptoms and side effects. To which, the last theme “Handling contextual influencing experiences after cancer treatment” displayed post-treatment emotions of being “Shocked and disappointed” and “Concerned and unsupported” but also “Grateful and forward-thinking”, where strategies such as “Appreciating Life”, “Networking socially,” and “Adapting to the new life” were used.

Conclusions

The results indicated the need for a more patient-centered care approach, with clearer structures and improved individual support both before and after treatment and in connection to rehabilitation. Patients’ cognitive changes after cancer treatment should be considered in the aftercare, which should also include adaptation to situation and strengthening of patients’ self-management as a goal.
The aqueous extract of Artemisia Absinthium L. stimulates HO-1/MT-1/Cyp450 signaling pathway via oxidative stress regulation induced by aluminium oxide nanoparticles (α and γ) animal model
Authors: Karami Esmaeil , Goodarzi Zahra , Shahtaheri Seyed Jamaleddin , Kiani Mehrafarin , Faridan Mohammad , Ghazi-Khansari Mahmoud
Published: September 2023

Background

This research aimed to evaluate the protective effects of Artemisia Absinthium L. (Abs) against liver damage induced by aluminium oxide nanoparticles (Al2O3 NPs) in rats, including both structural and functional changes associated with hepatotoxicity.

Methods

Thirty-six rats were randomly divided into six groups (n = 6). The first group received no treatment. The second group was orally administered Abs at a dose of 200 mg/kg/b.w. The third and fifth groups were injected intraperitoneally with γ-Al2O3 NPs and α-Al2O3 NPs, respectively, at a dose of 30 mg/kg/b.w. The fourth and sixth groups were pre-treated with oral Abs at a dose of 200 mg/kg/b.w. along with intraperitoneal injection of γ-Al2O3 NPs and α-Al2O3 NPs, respectively, at a dose of 30 mg/kg/b.w.

Results

Treatment with γ-Al2O3 NPs resulted in a significant decrease (P < 0.05) in total body weight gain, relative liver weight to body weight, and liver weight in rats. However, co-administration of γ-Al2O3 NPs with Abs significantly increased body weight gain (P < 0.05). Rats treated with Al2O3 NPs (γ and α) exhibited elevated levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), alanine transaminase (ALT), and aspartate aminotransferase (AST). Conversely, treatment significantly reduced glutathione peroxidase (GPx), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (TAC) levels compared to the control group. Furthermore, the expression of heme oxygenase-1 (HO-1) and metallothionein-1 (MT-1) mRNAs, cytochrome P450 (CYP P450) protein, and histopathological changes were significantly up-regulated in rats injected with Al2O3 NPs. Pre-treatment with Abs significantly reduced MDA, AST, HO-1, and CYP P450 levels in the liver, while increasing GPx and T-SOD levels compared to rats treated with Al2O3 NPs.

Conclusion

The results indicate that Abs has potential protective effects against oxidative stress, up-regulation of oxidative-related genes and proteins, and histopathological alterations induced by Al2O3 NPs. Notably, γ-Al2O3 NPs exhibited greater hepatotoxicity than α-Al2O3 NPs.
Utilization of patient portals: a cross-sectional study investigating associations with mobile app quality
Authors: El Yaman Noha , Zeitoun Jad , Diab Rawan , Mdaihly Mohamad , Diab Razan , Kobeissi Lynn , Abou Ljoud Salwa , Antoun Jumana , Bardus Marco
Published: September 2023

Background

Mobile apps facilitate patients’ access to portals and interaction with their healthcare providers. The COVID-19 pandemic accelerated this trend globally, but little evidence exists on patient portal usage in the Middle East, where internet access and digital literacy are limited. Our study aimed to explore how users utilize a patient portal through its related mobile app (MyChart by EPIC).

Methods

We conducted a cross-sectional survey of MyChart users, recruited from a tertiary care center in Lebanon. We collected MyChart usage patterns, perceived outcomes, and app quality, based on the Mobile Application Rating Scale (user version, uMARS), and sociodemographic factors. We examined associations between app usage, app quality, and sociodemographic factors using Pearson’s correlations, Chi-square, ANOVA, and t-tests.

Results

428 users completed the survey; they were primarily female (63%), aged 41.3 ± 15.6 years, with a higher education level (87%) and a relatively high crowding index of 1.4 ± 0.6. Most of the sample was in good and very good health (78%) and had no chronic illnesses (67%), and accessed the portal through MyChart once a month or less (76%). The most frequently used features were accessing health records (98%), scheduling appointments (67%), and messaging physicians (56%). According to uMARS completers (n = 200), the objective quality score was 3.8 ± 0.5, and the subjective quality was 3.6 ± 0.7. No significant association was found between overall app usage and the mobile app quality measured via uMARS. Moreover, app use frequency was negatively associated with education, socioeconomic status, and perceived health status. On the other hand, app use was positively related to having chronic conditions, the number of physician visits and subjective app quality.

Conclusion

The patient portal usage was not associated with app quality but with some of the participants’ demographic factors. The app offers a user-friendly, good-quality interface to patient health records and physicians, appreciated chiefly by users with relatively low socioeconomic status and education. While this is encouraging, more research is needed to capture the usage patterns and perceptions of male patients and those with even lower education and socioeconomic status, to make patient portals more inclusive.
‘It’s not like real therapy’: young people receiving child welfare services’ experiences of video consultations in mental healthcare in Norway: a mixed methods approach
Authors: Krane Vibeke , Kaasbøll Jannike , Kaspersen Silje L. , Ådnanes Marian
Published: September 2023

Background

Video consultations has been suggested to lower the threshold for child and adolescent mental healthcare treatment. This study explores how young people receiving child welfare services experience video consultations in child and adolescent mental healthcare. The study is part of a larger Norwegian study of access to health services for this target group.

Methods

The study has a mixed methods design including qualitative interviews and a quantitative survey, with young people receiving child welfare services. The qualitative interviews included 10 participants aged 15–19. The survey included 232 participants aged 16–24 of which 36 reported having received video consultations in mental healthcare. The interviews were analysed using thematic analysis. The survey data was presented as frequencies to clarify the distribution of positive and negative perceptions of video consultation.

Results

The results show that the participants experienced video consultations as more superficial and less binding, compared to in-person sessions. They raised concerns of the therapeutic relationship, however some found it easier to regulate closeness and distance. In the survey several reported that their relationship with the therapist got worse, and that it was much more difficult to talk on screen. Moreover, a large proportion (42%) claimed that video consultations did not fit their treatment needs overall. However, a minority of the participants found it easier to talk to the therapist on screen.

Conclusions

The study reveals important weaknesses and disadvantages of online therapy as experienced by young people receiving child welfare services. It is particularly worrying that their criticism involves the relational aspects of treatment, as children receiving child welfare services often have relational experiences which make them particularly sensitive to challenges in relationships. This study shows that youth involvement in decision making of video consultations in therapy has been rare. Clinicians should be aware of these young people’s doubts regarding the quality of video consultations in child and adolescent mental health care. Further studies should examine how user involvement can be incorporated in video consultations in therapy and how this could improve experiences and the quality of video consultations.
A holistic model of health inequalities for health policy and state administration: a case study in the regions of the Czech Republic
Authors: Hübelová Dana , Caha Jan , Janošíková Lenka , Kozumplíková Alice
Published: September 2023

Background

Health inequities exist within and between societies at different hierarchical levels. Despite overall improvements in health status in European Union countries, disparities persist among socially, economically, and societally disadvantaged individuals. This study aims to develop a holistic model of health determinants, examining the complex relationship between various determinants of health inequalities and their association with health condition.

Methods

Health inequalities and conditions were assessed at the territorial level of Local Administrative Units (LAU1) in the Czech Republic. A dataset of 57 indicators was created, categorized into seven determinants of health and one health condition category. The necessary data were obtained from publicly available databases. Comparisons were made between 2001–2003 and 2016–2019. Various methods were employed, including composite indicator creation, correlation analysis, the Wilcoxon test, aggregate index calculation, cluster analysis, and data visualization using the LISA method.

Results

The correlation matrix revealed strong relationships between health inequality categories in both periods. The most significant associations were observed between Economic status and social protection and Education in the first period. However, dependencies weakened in the later period, approaching values of approximately 0.50. The Wilcoxon test confirmed variations in determinant values over time, except for three specific determinants. Data visualization identified persistently adverse or worsening health inequalities in specific LAU1, focusing on categories such as Economic status and social protection, Education, Demographic situation, Environmental status, Individual living status, and Road safety and crime. The health condition indices showed no significant change over time, while the aggregate index of health inequalities improved with widened differences.

Conclusion

Spatial inequalities in health persist in the Czech Republic, influenced by economic, social, demographic, and environmental factors, as well as local healthcare accessibility. Both inner and outer peripheries exhibit poor health outcomes, challenging the assumption that urban areas fare better. The combination of poverty and vulnerabilities exacerbates these inequalities. Despite the low rates of social exclusion and poverty, regional health inequalities persist in the long term. Effectively addressing health inequalities requires interdisciplinary collaboration and evidence-based policy interventions. Efforts should focus on creating supportive social and physical environments, strengthening the healthcare system, and fostering cooperation with non-medical disciplines.
Triglyceride glucose-body mass index and cardiovascular mortality in patients undergoing peritoneal dialysis: a retrospective cohort study
Authors: Zhan Cuixia , Peng Yuan , Ye Hongjian , Diao Xiangwen , Yi Chunyan , Guo Qunying , Chen Wei , Yang Xiao
Published: September 2023

Background

Recent studies have shown that triglyceride glucose-body mass index (TyG-BMI) is associated with the risk of ischemic stroke and coronary artery disease. However, little attention has been given to the association between TyG-BMI and cardiovascular disease (CVD) mortality in patients undergoing peritoneal dialysis (PD). Therefore, this study aimed to explore the relationship between TyG-BMI and CVD mortality in southern Chinese patients undergoing PD.

Methods

Incident patients receiving PD from January 1, 2006, to December 31, 2018, with baseline serum triglyceride, glucose, and body mass index (BMI) information, were recruited for this single-center retrospective cohort study. TyG-BMI was calculated based on fasting plasma glucose, triglyceride, and BMI values. The association between TyG-BMI, CVD and all-cause mortality was evaluated using a multivariate-adjusted Cox proportional hazard regression model.

Results

Of 2,335 patients, the mean age was 46.1 ± 14.8 years; 1,382 (59.2%) were male, and 564 (24.2%) had diabetes. The median TyG-BMI was 183.7 (165.5–209.2). Multivariate linear regression showed that advanced age, male sex, history of CVD, higher levels of albumin and low-density lipoprotein cholesterol, and higher urine output were correlated with a higher TyG-BMI (P < 0.05). During a median follow-up period of 46.6 (22.4–78.0) months, 615 patients died, of whom 297 (48.2%) died as a result of CVD. After adjusting for demographics and comorbidities, TyG-BMI was significantly associated with an increased risk of CVD mortality (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.05–2.17) and all-cause mortality (HR 1.36, 95% CI 1.05–1.75). After full adjustment, the 28% risk of CVD mortality (HR 1.28, 95% CI 1.13–1.45) and 19% risk of all-cause mortality were elevated (HR 1.19, 95% CI 1.09–1.31) when TyG-BMI increased by 1 stand deviation (SD) (34.2).

Conclusions

A higher baseline TyG-BMI was independently associated with an increased risk of CVD and all-cause mortality in patients receiving PD.
Retrospective analysis of the endometrial preparation protocols for frozen-thawed embryo transfer cycles in women with endometriosis
Authors: Yang Jingdi , Wen Yangxing , Li Danping , Hou Xuerong , Peng Bo , Wang Zengyan
Published: September 2023

Background

There was inconsistency in optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) in patients with endometriosis. We conducted this study to investigate the effect of different endometrial preparation protocols on the pregnancy outcomes in patients with endometriosis undergoing FET cycles, and determine the optimal number of GnRHa injections in GnRHa-HRT protocols.

Method(s)

This was a retrospective cohort analysis of women with endometriosis who underwent FET cycles at a single university-based center. This study retrospectively analyzed 2048 FET cycles in our center from 2011 to 2020. According to the endometrial preparation protocols, patients were divided into 4 groups: gonadotropin releasing hormone agonist-hormone replacement therapy(GnRHa-HRT), hormone replacement therapy(HRT), ovulation induction(OI), and natural cycle(NC). In the GnRHa-HRT group, patients were further divided into 3 groups: one injection of GnRHa, two injections of GnRHa, and three or more injections of GnRHa. The primary outcome was the clinical pregnancy rate. Propensity score matching was used to adjust for potential non-similarities among the groups. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy outcomes.

Result(s)

There were no statistical differences in pregnancy outcomes among the four endometrial preparation protocols in FET cycles with endometriosis patients, the results retained after propensity score matching(PSM). And in endometriosis patients complicated with adenomyosis, the results remained similar. In patients with GnRHa-HRT protocol, there were no differences in clinical pregnancy rate and live birth rate with different numbers of GnRHa injections, the early miscarriage rate were 18% in the two injections of GnRHa group and 6.5% in the one injection of GnRHa group(P = 0.017). Multifactorial logistic regression analysis showed that two injections of GnRHa before FET was associated with increased early miscarriage rate compared with one injection of GnRHa[adjusted OR (95% CI): 3.116(1.079–8.998),p = 0.036].

Conclusion(s)

The four kinds of endometrial preparation protocols for FET, GnRHa-HRT, HRT, OI and NC had similar pregnancy outcomes in patients with endometriosis. In endometriosis patients complicated with adenomyosis, the results remained similar. In patients with endometriosis undergoing GnRHa-HRT protocol for FET, more injections of GnRHa had no more advantages in pregnancy outcomes, on the contrary, it might increase the early miscarriage rate.
Equity assessment of maternal and child healthcare benefits utilization and distribution in public healthcare facilities in Bangladesh: a benefit incidence analysis
Authors: Sheikh Nurnabi , Sultana Marufa , Sarker Abdur Razzaque , Morton Alec
Published: September 2023

Background

The distribution of healthcare services should be based on the needs of the population, regardless of their ability to pay. Achieving universal health coverage implies first ensuring that people of all income levels have access to quality healthcare, and then allocating resources reasonably considering individual need. Hence, this study aims to understand how public benefits in Bangladesh are currently distributed among wealth quintiles considering different layers of healthcare facilities and to assess the distributional impact of public benefits.

Methods

To conduct this study, data were extracted from the recent Bangladesh Demographic and Health Survey 2017–18. We performed benefit incidence analysis to determine the distribution of maternal and child healthcare utilization in relation to wealth quintiles. Disaggregated and national-level public benefit incidence analysis was conducted by the types of healthcare services, levels of healthcare facilities, and overall utilization. Concentration curves and concentration indices were estimated to measure the equity in benefits distribution.

Results

An unequal utilization of public benefits observed among the wealth quintiles for maternal and child healthcare services across the different levels of healthcare facilities in Bangladesh. Overall, upper two quintiles (richest 19.8% and richer 21.7%) utilized more benefits from public facilities compared to the lower two quintiles (poorest 18.9% and poorer 20.1%). Benefits utilization from secondary level of health facilities was highly pro-rich, while benefit utilization found pro-poor at primary levels. The public benefits in Bangladesh were also not distributed according to the needs of the population; nevertheless, poorest 20% household cannot access 20% share of public benefits in most of the maternal and child healthcare services even if we ignore their needs.

Conclusions

Benefit incidence analysis in public health spending demonstrates the efficacy with which the government allocates constrained health resources to satisfy the needs of the poor. Public health spending in Bangladesh on maternal and child healthcare services were not equally distributed among wealth quintiles. Overall health benefits were more utilized by the rich relative to the poor. Hence, policymakers should prioritize redistribution of resources by targeting the socioeconomically vulnerable segments of the population to increase their access to health services to meet their health needs.
Proteomic analysis unveils Gb3-independent alterations and mitochondrial dysfunction in a gla−/− zebrafish model of Fabry disease
Authors: Elsaid Hassan Osman Alhassan , Rivedal Mariell , Skandalou Eleni , Svarstad Einar , Tøndel Camilla , Birkeland Even , Eikrem Øystein , Babickova Janka , Marti Hans-Peter , Furriol Jessica
Published: September 2023

Background

Fabry disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene, resulting in reduced or lack of α-galactosidase A activity. This results in the accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in lysosomes causing cellular impairment and organ failures. While current therapies focus on reversing Gb3 accumulation, they do not address the altered cellular signaling in FD. Therefore, this study aims to explore Gb3-independent mechanisms of kidney damage in Fabry disease and identify potential biomarkers.

Methods

To investigate these mechanisms, we utilized a zebrafish (ZF) gla−/− mutant (MU) model. ZF naturally lack A4GALT gene and, therefore, cannot synthesize Gb3. We obtained kidney samples from both wild-type (WT) (n = 8) and MU (n = 8) ZF and conducted proteome profiling using untargeted mass spectrometry. Additionally, we examined mitochondria morphology and cristae morphology using electron microscopy. To assess oxidative stress, we measured total antioxidant activity. Finally, immunohistochemistry was conducted on kidney samples to validate specific proteins.

Results

Our proteomics analysis of renal tissues from zebrafish revealed downregulation of lysosome and mitochondrial-related proteins in gla−/− MU renal tissues, while energy-related pathways including carbon, glycolysis, and galactose metabolisms were disturbed. Moreover, we observed abnormal mitochondrial shape, disrupted cristae morphology, altered mitochondrial volume and lower antioxidant activity in gla−/− MU ZF.

Conclusions

These results suggest that the alterations observed at the proteome and mitochondrial level closely resemble well-known GLA mutation-related alterations in humans. Importantly, they also unveil novel Gb3-independent pathogenic mechanisms in Fabry disease. Understanding these mechanisms could potentially lead to the development of innovative drug screening approaches. Furthermore, the findings pave the way for identifying new clinical targets, offering new avenues for therapeutic interventions in Fabry disease. The zebrafish gla−/− mutant model proves valuable in elucidating these mechanisms and may contribute significantly to advancing our knowledge of this disorder.

Graphical Abstract
Microglial SIRT1 activation attenuates synapse loss in retinal inner plexiform layer via mTORC1 inhibition
Authors: Yao Ke , Mou Qianxue , Lou Xiaotong , Ye Meng , Zhao Bowen , Hu Yuanyuan , Luo Jing , Zhang Hong , Li Xing , Zhao Yin
Published: September 2023

Background

Optic nerve injury (ONI) is a key cause of irreversible blindness and triggers retinal ganglion cells (RGCs) change and synapse loss. Microglia is the resistant immune cell in brain and retina and has been demonstrated to be highly related with neuron and synapse injury. However, the function of Sirtuin 1 (SIRT1), a neuroprotective molecule, in mediating microglial activation, retinal synapse loss and subsequent retinal ganglion cells death in optic nerve injury model as well as the regulatory mechanism remain unclear.

Method

To this end, optic nerve crush (ONC) model was conducted to mimic optic nerve injury. Resveratrol and EX527, highly specific activator and inhibitor of SIRT1, respectively, were used to explore the function of SIRT1 in vivo and vitro. Cx3Cr1-CreERT2/RaptorF/Fmice were used to delete Raptor for inhibiting mammalian target of rapamycin complex 1 (mTORC1) activity in microglia. HEK293 and BV2 cells were transfected with plasmids to explore the regulatory mechanism of SIRT1.

Results

We discovered that microglial activation and synapse loss in retinal inner plexiform layer (IPL) occurred after optic nerve crush, with later-development retinal ganglion cells death. SIRT1 activation induced by resveratrol inhibited microglial activation and attenuated synapse loss and retinal ganglion cells injury. After injury, microglial phagocytosed synapse and SIRT1 inhibited this process to protect synapse and retinal ganglion cells. Moreover, SIRT1 exhibited neuron protective effects via activating tuberous sclerosis complex 2 (TSC2) through deacetylation, and enhancing the inhibition effect of tuberous sclerosis complex 2 on mammalian target of rapamycin complex 1 activity.

Conclusion

Our research provides novel insights into microglial SIRT1 in optic nerve injury and suggests a potential strategy for neuroprotective treatment of optic nerve injury disease.
Together4RD position statement on collaboration between European reference networks and industry
Authors: Hedley Victoria , Bolz-Johnson Matt , Hernando Ines , Kenward Rosalind , Nabbout Rima , Romero Clara , Schaefer Franz , Upadhyaya Sheela ,   Together4RD Steering Group, Arzimanoglou Alexis , Dollfus Hélène , Leroux Dorothée , Scarpa Maurizio , Schaefer Franz , Verloes Alain , Bolz-Johnson Matt , Daria Julkowska  , Rath Ana , Hedley Victoria , Ussi Anton , Mimouni Yanis , Nabbout Rima , Cuisenier Morgane , Chalandon Anne-Sophie , Digneffe Toon , Almberg Gabriella , Scarabelli Matteo , Vranken Leander
Published: September 2023

Notwithstanding two decades of policy and legislation in Europe, aimed to foster research and development in rare conditions, only 5–6% of rare diseases have dedicated treatments. Given with the huge number of conditions classed as rare (which is increasing all the time), this equates to major unmet need for patients (over 30 million in the EU alone). Worryingly, the pace of Research and Innovation in Europe is lagging behind other regions of the world, and a seismic shift in the way in which research is planned and delivered is required, in order to remain competitive and—most importantly—bring meaningful, disease-altering treatments to those who desperately need them. The European Reference Networks (ERNs), launched in 2017, hold major potential to alleviate many of these challenges, and more, but only if adequately supported (financially, technically, and via robust policies and infrastructure) to realise that potential: and even then, only if able to forge robust collaborations harnessing the expertise, resources, knowledge and data of all stakeholders involved in rare disease, including Industry. To-date, however, ERN-Industry interactions have been largely limited, for a range of reasons (concerning barriers both tangible and perceived). This Position Statement analyses these barriers, and explains how Together4RD is seeking to move the needle here, by learning from case studies, exploring frameworks for collaboration, and launching pilots to explore how best to plan and deliver multistakeholder interactions addressing real research needs.
Can a shoe‐mounted IMU identify the effects of orthotics in ways comparable to gait laboratory measurements?
Authors: Lewin Max , Price Carina , Nester Christopher
Published: September 2023

Background

Footwear and orthotic research has traditionally been conducted within laboratories. With increasing prevalence of wearable sensors for foot and ankle biomechanics measurement, transitioning experiments into the real‐world is realistic. However wearable systems must effectively detect the direction and magnitude of response to interventions to be considered for future usage.

Methods

RunScribe IMU was used simultaneously with motion capture, accelerometers, and force plates during straight‐line walking. Three orthotics (A, B, C) were used to change lower limb biomechanics from a control (SHOE) including: Ground reaction force (GRF) loading rate (A), pronation excursion (A and B), maximum pronation velocity (A and B), and impact shock (C) to test whether RunScribe detected effects consistent with laboratory measurements. Sensitivity was evaluated by assessing: 1. Significant differences (t‐test) and effect sizes (Cohen's d) between measurement systems for the same orthotic, 2. Statistical significance (t‐test and ANOVA) and effect size (Cohen's d & f) for orthotic effect across measurement systems 3. Direction of orthotic effect across measurement systems.

Results

GRF loading rate (SHOE: p = 0.138 d = 0.403, A: p = 0.541 d = 0.165), impact shock (SHOE: p = 0.177 d = 0.405, C: p = 0.668 d = 0.132), pronation excursion (A: p = 0.623 d = 0.10, B: p = 0.986 d = 0.00) did not significantly differ between measurement systems with low effect size. Significant differences and high effect sizes existed between systems in the control condition for pronation excursion (p = 0.005 d = 0.68), and all conditions for pronation velocity (SHOE: p < 0.001 d = 1.24, A: p = 0.001 p = 1.21, B: p = 0.050 d = 0.64).

RunScribe (RS) and Laboratory (LM) recorded the same significant effect of orthotic but inconsistent effect sizes for GRF loading rate (LM:p = 0.020 d = 0.54, RS: p = 0.042 d = 0.27), pronation excursion (LM: p < 0.001 f = 0.31, RS: p = 0.042 f = 0.15), and non‐significant effect of orthotic for impact shock (LM: p = 0.182 d = 0.08, RS: p = 0.457 d = 0.24). Statistical significance was different between systems for effect of orthotic on pronation velocity (LM: p = 0.010 f = 0.18, RS: p = 0.093 f = 0.25).

RunScribe and Laboratory agreed on the direction of change of the biomechanics variables for 69% (GRF loading rate), 40%—70% (pronation excursion), 47%—65% (pronation velocity), and 58% (impact shock) of participants.

Conclusion

The RunScribe shows sensitivity to orthotic effect consistent with the laboratory at the group level for GRF loading rate, pronation excursion, and impact shock during walking. There were however large discrepancies between measurements in individuals. Application of the RunScribe for group analysis may be appropriate, however implementation of RunScribe for individual assessment and those including pronation may lead to erroneous interpretation.
Early occurrence of acute myelomonocytic leukemia (M4/M5) after liver transplantation: a case report
Authors: Zamani Farhad , Karimi Hanie , Mansoorian Mohsenreza , Basi Ali , Hosseini S. Ahmad , Zahed Zahra , Seyedghasemipour Nasim , Sahraie Roghayeh
Published: September 2023

Introduction

Acute myeloid leukemia is a rare event in post-liver-transplantation recipients. In the present report, we described a case of extramedullary acute myeloid leukemia, M4/M5 subtype, following orthotopic liver transplant.

Case presentation

The patient was a 50-year-old Iranian woman who underwent orthotopic liver transplant due to hepatitis B-related cirrhosis (Child C, MELD (model for end-stage liver disease score) = 22). Orthotopic liver transplant was performed using the piggy back technique in January 2022. Induction immunosuppressive therapy was 1 gm methylprednisolone for 3 days followed by a triple maintenance immunosuppressive regimen including mycophenolate mofetil, prednisolone, and tacrolimus. About 5 months after orthotopic liver transplant in June 2022, the patient presented with leukocytosis, with white blood cell count of 99.4 × 103/µl, and physical examination revealed only cervical lymphadenopathy. Biopsy of cervical lymph nodes showed a myeloid tumor. She was immediately hospitalized. Eight hours after hospitalization, the patient gradually developed lethargy and decreased O2 saturation to approximately 89%. Flow cytometry demonstrated the markers of a myelomonocytic acute myeloid leukemia (M4/M5). Cytoreduction was immediately started by intensive leukopheresis followed by induction therapy. Because of a septic complication during the induction therapy, further chemotherapy was discontinued and broad-spectrum antibiotics and antifungal treatments started. Unfortunately, our patient died of severe septic shock 42 days after hospitalization.

Conclusion

Acute myeloid leukemia is a rare phenomenon after liver transplantation, and it can follow a rapidly fatal clinical course.