bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of menopausal symptoms and attitudes towards menopausal hormone therapy in women aged 40–60 years: a cross-sectional study
Authors: Lu Jie , Li Kangfen , Zheng Xinlie , Liu Ran , Chen Min , Xian Jingyun , Tu Suhua , Xie Lingling
Published: September 2023

Background

Menopause is a specific physical and psychological transition period for women, during which they experience a series of menopausal symptoms. Menopausal hormone therapy is an important treatment for improving menopausal symptoms. Helping women correctly understand menopausal hormone therapy is a prerequisite for increasing the acceptance and utilization of menopausal hormone therapy by women. Physical examinations are an important method for women to master their own health status and detect potential health problems, and in recent years, an increasing number of women have actively participated in physical examinations. Therefore, this study aims to comprehend the prevalence of menopausal symptoms and attitudes towards menopausal hormone therapy among women aged 40–60 who underwent physical examinations, which would provide a useful reference to reduce the prevalence of menopausal symptoms and improve acceptance of menopausal hormone therapy.

Methods

This cross-sectional study was conducted at the Health Management Centre of the Affiliated Hospital of Southwest Medical University in Luzhou City, Sichuan Province. The data were collected from 295 women aged between 40 and 60 using convenience sampling. Information on all participants was collected through face-to-face interviews. Participants completed a demographic questionnaire and an attitude towards menopausal hormone therapy questionnaire, and the modified Kupperman index was used to assess the prevalence and severity of participants' menopausal symptoms. The collected data were processed using SPSS and Excel software and analysed using descriptive statistics and logistic regression.

Results

The top 5 menopausal symptoms were insomnia, fatigue, bone and joint pain, sexual dysfunction and emotional instability. Multiple linear regression analysis showed that residence, sexual intercourse frequency, mentality, and physical exercise were the influencing factors of menopausal symptoms. The study showed that 77% of women said they were still reluctant to receive menopausal hormone therapy after experiencing menopause-related symptoms. The main source of menopausal hormone therapy-related knowledge among women was from surrounding menopausal women (62%), and 54% wanted to gain menopausal hormone therapy-related knowledge through a web-based approach.

Conclusion

The incidence of menopausal symptoms is higher in women aged 40–60 years, which is related to women’s mentality, exercise, and sexual intercourse frequency. In addition, the results of this study indicate that women’s knowledge of menopausal hormone therapy is insufficient, which suggests that we need to strengthen health education to improve the acceptance rate of menopausal hormone therapy.
Medical interns in district health services: an evaluation of the new family medicine rotation in the Western Cape of South Africa
Authors: Hutton Lauren , Jenkins Louis Stander , Mash Robert , von Pressentin Klaus , Reid Steve , Morgan Jennie , Kapp Paul
Published: September 2023

Background

In 2021, South Africa introduced a 6-month internship rotation in family medicine, in the second year of a 2-year internship programme for newly qualified doctors. This was a major change from the previous 3-months training in family medicine, and expanded the training platform to smaller district hospitals and primary health care (PHC) facilities, many of which had never had interns. The medical disciplines in South Africa needed to know if this change in the internship programme was worthwhile and successful. The aim of this study was to assess the new family medicine rotation for medical interns at district health facilities in the Western Cape Province.

Methods

Descriptive exploratory qualitative research included six intern programmes across the province. Purposeful sampling identified a heterogeneous group with maximum variation in experience. Overall, eight interns, four managers, four supervisors and four intern curators were included. Individual semi-structured interviews were audio-recorded and the transcripts were thematically analysed using the framework method and Atlas-ti software.

Results

Four major themes emerged around the varied structure and organisational characteristics of the rotations, the orientation and arrival of interns, their learning during the rotation, and impact on health services. A programme theory was developed that defined the key inputs (i.e. infrastructure, communication, orientation, preparation, prior learning and guidelines), processes (i.e. model of the rotation, clinical training and supervision, clinical teaching), outputs (i.e. more independent decision making, approach to undifferentiated problems, approach to chronic care and continuity, development of procedural skills, approach to sequential coordination of care and referrals, working in a multidisciplinary team and inter-professional learning, integration of multiple competencies, as well as becoming more person and community orientated).

Conclusions

The new rotation in family medicine was positively experienced by most interns, supervisors and managers. It should lead to improved quality of care, better preparation for obligatory community service, and an increased likelihood of considering a career in district level health services. This study will form part of an exploratory sequential mixed methods study that incorporates the key issues into a questionnaire for a descriptive survey of all interns in a subsequent study.
Entrustable professional activities (EPAs) for undergraduate medical education – development and exploration of social validity
Authors: Gummesson Christina , Alm Stina , Cederborg Anna , Ekstedt Mattias , Hellman Jarl , Hjelmqvist Hans , Hultin Magnus , Jood Katarina , Leanderson Charlotte , Lindahl Bertil , Möller Riitta , Rosengren Björn , Själander Anders , Svensson Peter J , Särnblad Stefan , Tejera Alexander
Published: September 2023

Background

The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders.

Aim

The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs.

Method and material

In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater’s perception of the present graduates’ required level of supervision when performing the activity. Free-text comments were also included and analyzed.

Results

Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as “important” by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported “independent”. The three themes of the free text comments were: ‘relevant target areas and content’; ‘definition of the activities’; and ‘clinical practice and learning’.

Conclusion

Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.
Translation, cultural adaptation and validation of the General Medication Adherence Scale (GMAS) in moroccan patients with type-2 diabetes
Authors: Maryem Arraji , Younes Iderdar , Yassmine Mourajid , Morad Guennouni , Karima Boumendil , Amal Korrida , Noureddine El Khoudri , Mohamed Ifleh , Mohamed Khalis , Chahboune Mohamed
Published: September 2023

Background

The objective of the study was to cross-culturally adapt and validate the General Medication Adherence Scale (GMAS) in patients with type-2 diabetes in Morocco.

Methods

The study was a cross-sectional study conducted between September 12 and October 12, 2022, and included patients with type-2 diabetes from a primary health care network. To measure the different psychometric parameters of the construct, data analysis was performed using SPSS v20. The study was approved by the Moroccan Association for Research and Ethics.

Results

A total of 284 patients were included in the study; the results of the different psychometric parameters were largely acceptable. Indeed, the improvement of the goodness-of-fit of the model in relation to the independence model was evaluated by the comparative fit index (CFI), which was higher than 0.95, as well as the normalized fit index (NFI), which expresses the percentage of the general covariance between the variable demonstrated via the tested model when the null model is taken as reference and was also higher than 0.95 in this study. Additionally, the Tucker Louis Index (TLI) or Unstandardized Fit Index, which measures the increase in goodness of fit when moving from the reference model to the model under study, had a value of > 0.95. The correlations between the items were good; indeed, the Kaiser-Meyer-Olkin (KMO) index was > 0.7. The translated tool presents good internal consistency; thus, Cronbach’s α had a value of approximately 0.804 (> 0.7).

Conclusions

The version of the GMAS tool adapted to the Moroccan context has very acceptable psychometric values. This means that Moroccan researchers and health professionals can use it as an instrument to measure adherence among individuals with type-2 diabetes.
Identifying critical gaps in research to advance global surgery by 2030: a systematic mapping review
Authors: Kebede Meskerem Aleka , Tor Deng Simon Garang , Aklilu Tesfamariam , Petros Adane , Ifeanyichi Martilord , Aderaw Ezekiel , Bognini Maeve Sophia , Singh Darshita , Emodi Rosemary , Hargest Rachel , Friebel Rocco
Published: September 2023

Progress on surgical system strengthening has been slow due to a disconnect between evidence generation and the information required for effective policymaking. This systematic mapping review sought to assess critical research gaps in the field of global surgery guided by the World Health Organisation Health Systems building block framework, analysis of authorship and funding patterns, and an exploration of emerging research partnership networks. Literature was systematically mapped to identify, screen, and synthesize results of publications in the global surgery field between 2015 and March 2022. We searched four databases and included literature published in seven languages. A social network analysis determined the network attributes of research institutions and their transient relationships in shaping the global surgery research agenda. We identified 2,298 relevant studies out of 92,720 unique articles searched. Research output increased from 453 in 2015-16 to 552 in 2021-22, largely due to literature on Covid-19 impacts on surgery. Sub-Saharan Africa (792/2298) and South Asia (331/2298) were the most studied regions, although high-income countries represented a disproportionate number of first (42%) and last (43%) authors. Service delivery received the most attention, including the surgical burden and quality and safety of services, followed by capacity-building efforts in low- and middle-income countries. Critical research in economics and financing, essential infrastructure and supplies, and surgical leadership necessary to guide policy decisions at the country level were lacking. Global surgical systems remain largely under-researched. Knowledge diffusion requires an emphasis on developing sustainable research partnerships and capacity across low- and middle-income countries. A renewed focus must be given to equipping countries with tools for effective decision-making to enhance investments in high-quality surgical services.
Increased paternal corticosterone exposure influences offspring behaviour and expression of urinary pheromones
Authors: Hoffmann Lucas B. , McVicar Evangeline A. , Harris Rebekah V. , Collar-Fernández Coralina , Clark Michael B. , Hannan Anthony J. , Pang Terence Y.
Published: September 2023

Background

Studies have shown that paternal stress prior to conception can influence the innate behaviours of their offspring. The evolutionary impacts of such intergenerational effects are therefore of considerable interest. Our group previously showed in a model of daily stress that glucocorticoid treatment of adult male mouse breeders prior to conception leads to increased anxiety-related behaviours in male offspring. Here, we aimed to understand the transgenerational effects of paternal stress exposure on the social behaviour of progeny and its potential influence on reproductive success.

Results

We assessed social parameters including social reward, male attractiveness and social dominance, in the offspring (F1) and grand-offspring (F2). We report that paternal corticosterone treatment was associated with increased display of subordination towards other male mice. Those mice were unexpectedly more attractive to female mice while expressing reduced levels of the key rodent pheromone Darcin, contrary to its conventional role in driving female attraction. We investigated the epigenetic regulation of major urinary protein (Mup) expression by performing the first Oxford Nanopore direct methylation of sperm DNA in a mouse model of stress, but found no differences in Mup genes that could be attributed to corticosterone-treatment. Furthermore, no overt differences of the prefrontal cortex transcriptome were found in F1 offspring, implying that peripheral mechanisms are likely contributing to the phenotypic differences. Interestingly, no phenotypic differences were observed in the F2 grand-offspring.

Conclusions

Overall, our findings highlight the potential of moderate paternal stress to affect intergenerational (mal)adaptive responses, informing future studies of adaptiveness in rodents, humans and other species.
Fluorescence-tagged salivary small extracellular vesicles as a nanotool in early diagnosis of Parkinson’s disease
Authors: Rastogi Simran , Rani Komal , Rai Sanskriti , Singh Rishabh , Bharti Prahalad Singh , Sharma Vaibhav , Sahu Jyoti , Kapoor Vrinda , Vishwakarma Poorvi , Garg Sumit , Gholap Shivajirao Lahu , Inampudi Krishna Kishore , Modi Gyan Prakash , Rani Neerja , Tripathi Madhavi , Srivastava Achal , Rajan Roopa , Nikolajeff Fredrik , Kumar Saroj
Published: September 2023

Background

Parkinson’s disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery.

Methods

In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson’s disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography.

Results

We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112).

Conclusions

In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.

Graphical Abstract
Relationship between cumulative exposure to triglyceride-glucose index and heart failure: a prospective cohort study
Authors: Zheng Huancong , Chen Guanzhi , Wu Kuangyi , Wu Weiqiang , Huang Zegui , Wang Xianxuan , Chen Zekai , Cai Zefeng , Cai Zhiwei , Lan Yulong , Wu Shouling , Chen Youren
Published: September 2023

Background

High triglyceride-glucose index (TyG) is a major risk factor for heart failure, but the long-term effect of high TyG index on the risk of developing heart failure remains unclear. Therefore, we aimed to determine the relationship between the cumulative exposure to TyG index and the risk of heart failure.

Methods

A total of 56,149 participants from the Kailuan Study, who participated in three consecutive health examinations in 2006, 2008, and 2010 and had no history of heart failure or cancer were recruited for this study. The cumulative TyG index was calculated as the weighted sum (value × time) of the mean TyG index for each time interval. The participants were placed into quartiles based on their cumulative TyG index. The study ended on December 31, 2020, and the primary outcome was new-onset heart failure during the follow-up period. In addition, a Cox proportional hazards regression model and a restricted cubic spline analysis were used to further evaluate the relationship between cumulative TyG index and the risk of heart failure.

Results

During a median follow-up period of 10.04 years, a total of 1,312 new heart failure events occurred. After adjustment for potential confounding factors, the Cox regression analysis showed that the hazard ratios (95% confidence intervals) for the risk of heart failure in the Q2, Q3, and Q4 groups were 1.02 (0.83,1.25), 1.29 (1.07,1.56) and 1.40 (1.15,1.71), respectively, vs. the Q1 group. The subgroup analysis showed a significant interaction between cumulative TyG index and BMI or waist circumference, but there was no interaction between age, sex and cumulative TyG index. The restricted cubic spline analysis showed a dose-response relationship between cumulative TyG index and the risk of heart failure. In addition, the sensitivity analysis generated results that were consistent with the primary results.

Conclusions

High cumulative TyG index is associated with a higher risk of heart failure. Thus, the TyG index may be useful for the identification of individuals at high risk of heart failure. The present findings emphasize the importance of the long-term monitoring of the TyG index in clinical practice.
Metabolic engineering of fast-growing Vibrio natriegens for efficient pyruvate production
Authors: Wu Fengli , Wang Shucai , Peng Yanfeng , Guo Yufeng , Wang Qinhong
Published: September 2023

Background

Pyruvate is a widely used value-added chemical which also serves as a hub of various metabolic pathways. The fastest-growing bacterium Vibrio natriegens is a promising chassis for synthetic biology applications with high substrate uptake rates. The aim of this study was to investigate if the high substrate uptake rates of V. natriegens enable pyruvate production at high productivities.

Results

Two prophage gene clusters and several essential genes for the biosynthesis of byproducts were first deleted. In order to promote pyruvate accumulation, the key gene aceE encoding pyruvate dehydrogenase complex E1 component was down-regulated to reduce the carbon flux into the tricarboxylic acid cycle. Afterwards, the expression of ppc gene encoding phosphoenolpyruvate carboxylase was fine-tuned to balance the cell growth and pyruvate synthesis. The resulting strain PYR32 was able to produce 54.22 g/L pyruvate from glucose within 16 h, with a yield of 1.17 mol/mol and an average productivity of 3.39 g/L/h. In addition, this strain was also able to efficiently convert sucrose or gluconate into pyruvate at high titers.

Conclusion

A novel strain of V. natriegens was engineered which was capable to provide higher productivity in pyruvate synthesis. This study lays the foundation for the biosynthesis of pyruvate and its derivatives in fast-growing V. natriegens.
Polyurethane-based nanofibrous mat containing porphyrin with photosensitivity and bactericidal properties can promote cutaneous tissue healing in rats
Authors: Saghebasl Solmaz , Amini Hassan , Nobakht Abbas , Haiaty Sanya , Bagheri Hesam Saghaei , Hasanpour Parisa , Milani Morteza , Saghati Sepideh , Naturi Ozra , Farhadi Mehrdad , Rahbarghazi Reza
Published: September 2023

The regeneration of cutaneous tissue is one of the most challenging issues in human regenerative medicine. To date, several studies have been done to promote cutaneous tissue healing with minimum side effects. The healing potential of polyurethane (PU)/Poly (caprolactone)–poly (ethylene glycol)–poly (caprolactone) (PCEC)/chitosan (CS) (PCS) nanofibrous mat with cationic photosensitizer meso tetrakis (N-methyl pyridinium-4-yl) porphyrin tetratosylate salt (TMP) was examined. The CS tripolyphosphate nanoparticles (CSNPs) were prepared and loaded by TMP to provide an efficient drug release system (TMPNPs) for delivery of TMP to promote wound healing. In in vitro setting, parameters such as bactericidal effects, cytocompatibility, and hemolytic effects were examined. The healing potential of prepared nanofibrous mats was investigated in a rat model of full-thickness cutaneous injury. PCS/TMP/TMPNPs nanofibers can efficiently release porphyrin in the aqueous phase. The addition of TMPNPs and CS to the PU backbone increased the hydrophilicity, degradation, and reduced mechanical properties. The culture of human fetal foreskin fibroblasts (HFFF2) on PCS/TMP/TMPNPs scaffold led to an increased survival rate and morphological adaptation analyzed by MTT and SEM images. Irradiation with a red laser (635 nm, 3 J/cm2) for the 30 s reduced viability of S. aureus and E. Coli bacteria plated on PCS/TMP and PCS/TMP/TMPNPs nanofibrous mats compared to PU/PCEC (PC) and PU/PCEC/CS (PCS) groups, indicating prominent antibacterial effects of PCS/TMP and PCS/TMP/TMPNPs nanofibrous (p < 0.05). Data indicated that PCS/TMP/TMPNPs mat enhanced healing of the full-thickness excisional wound in a rat model by the reduction of inflammatory response and fibrotic changes compared to the PC, and PCS groups (p < 0.05). Immunofluorescence imaging indicated that levels of Desmoglein were increased in rats that received PCS/TMP/TMPNPs compared to the other groups. It is found that a PU-based nanofibrous mat is an appropriate scaffold to accelerate the healing of injured skin.

Graphical abstract
A Case report of a continuous ambulatory drug delivery (CADD) pump to deliver opioid agonist treatment in an acute care setting
Authors: Wigg Casey , Nolen Amy , Jauhal Lisa , Sharma Malika
Published: September 2023

Background

People with substance use disorder are at risk of complications of drug use and frequent hospitalization and may continue to use substances during admission to acute care. Acute care harm reduction strategies including oral or injectable prescription opioids may aid in care retention and improve health outcomes in this patient population.

Case presentation

A 58-year-old woman with refractory opioid use disorder was admitted to hospital for management of dysphagia secondary to esophageal stricture. She received injectable opioid agonist therapy using a continuous ambulatory drug delivery (CADD) pump in order to facilitate completion of her hospital admission.

Conclusions

The patient successfully received acute medical care with the use of a CADD pump for consistent, patient-controlled opioid administration, with the support of an interdisciplinary team and by respecting the patient’s own substance use goals.
Systems thinking in local government: intervention design and adaptation in a community-based study
Authors: Felmingham Tiana , O’Halloran Siobhan , Poorter Jaimie , Rhook Ebony , Needham Cindy , Hayward Joshua , Fraser Penny , Kilpatrick Stephanie , Leahy Deana , Allender Steven
Published: September 2023

Background

Systems thinking approaches are increasingly being used by communities to address complex chronic disease. This paper reports on the VicHealth Local Government Partnership (VLGP) which sought to co-create improvements in the health and well-being of children and young people by working with local government in Victoria, Australia.

Methods

The VLGP included a series of health promotion modules, aimed at creating policy, programme and practice changes across local government. One of these modules, Connecting the Dots – creating solutions for lasting change, aimed to build capacity for systems thinking in municipal public health and well-being planning across 13 councils. The approach was adapted and data were collected on the stimuli for, and results of, adaptation.

Results

The council adapted the systems thinking approach to meet geographic characteristics, priority health issue/s and participant target group needs. Adaptions applied to workshop materials, training delivery, existing and new resources, and to align with other community-based approaches. Stimuli for adaptation included the COVID-19 pandemic, needs of children and young people, capacity of council to deliver the workshop series, and time available within the project or for the participant group.

Conclusions

Systems thinking was used and adapted by councils to improve the health and well-being of children and young people and increase the voices of children and young people in decision-making. Flexible delivery is critical to ensure communities can adapt the approach to meet local needs.
The impact of macrosomia on cardiometabolic health in preteens: findings from the ROLO longitudinal birth cohort study
Authors: Callanan Sophie , Killeen Sarah Louise , Delahunt Anna , Cooney Nessa , Cushion Rosemary , McKenna Malachi J. , Crowley Rachel K. , Twomey Patrick J. , Kilbane Mark T. , McDonnell Ciara M. , Phillips Catherine M. , Cody Declan , McAuliffe Fionnuala M.
Published: September 2023

Background

Macrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty.

Methods

This is a secondary analysis of 9–11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann–Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes.

Results

In total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = − 0.095, 95% CI = − 0.162, − 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047).

Conclusion

This study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor.

Trial registration ISRCTN54392969 registered at www.isrctn.com.
Patterns in fish naming ability in two fishing communities of Myanmar
Authors: Si Aung , Kyawphyo Aung
Published: September 2023

Background

To date, there is little reliable information on the fish names used by two fishing communities of Myanmar, namely Intha (Inle Lake) and Rakhine (Bay of Bengal). Moreover, there have been no systematic studies on the distribution of fish-related traditional knowledge in these two communities. As there can be high levels of intra-community variation in traditional ecological knowledge, it is important to investigate this variation along the lines of key social variables.

Methods

Fieldwork was carried out in both communities and involved the presentation of visual stimuli (colour pictures of locally relevant fish species) to respondents, and asking for a name in the local language. The stimuli consisted of 43 and 218 fish species for Intha and Rakhine, respectively. The responses were analysed in terms of respondent age and occupation for both communities, plus village location for Intha and gender whenever both genders were represented in a sufficiently large number in the sample.

Results

Fish name lists were generated for both languages, taking into account lexical variation, as well as the number of people able to name each fish. The two communities differed markedly in the way fish knowledge was distributed. Overall, younger Intha knew fewer fish names, but there was little to no difference in fish knowledge among the Intha on the basis of occupation, location or gender. In contrast, the differences were very marked among Rakhine respondents.

Conclusions

The reduced fish knowledge of younger Intha may be ascribed to environmental disturbances that have caused many fish to go locally extinct. The otherwise homogenous distribution of fish knowledge in the Intha community may be due to the small number of species that people are required to learn. This idea needs to be tested with a larger sample of respondents. Among the Rakhine, a number of factors are responsible for the observed variation; these include a steep learning curve among younger fishermen, the difference in fish species encountered by fishermen and sellers, highly variable dietary preferences among the general populace and differing gender roles in the context of market visits. The authors are in full agreement with previous research that advocates a variationist approach to the study of traditional ecological knowledge.
Combined large cell neuroendocrine carcinoma, lung adenocarcinoma, and squamous cell carcinoma: a case report and review of the literature
Authors: Zhu Zirui , Liu You , Xu Hengliang , Ning Haoyong , Xia Yanmin , Shen Leilei
Published: September 2023

Background

Combined large cell neuroendocrine carcinoma (C-LCNEC) has a poor prognosis and there is no consensus about the treatment regimen for both LCNEC and C-LCNEC patients.

Case presentation

The patient was a 47-year-old female who received surgical resection. The postoperative histology and staging of the tumor suggested C-LCNEC with adenocarcinoma and squamous cell carcinoma and T2aN0M0 stage IB. Next-generation sequencing test showed KIF5B/RET fusion mutation without EGFR, ALK, RB1, and TP53 alterations. Adjuvant chemotherapy with 4-cycle docetaxel plus carboplatin was given and brain metastasis occurred after 10 months.

Conclusions

C-LCNEC with adenocarcinoma and squamous cell carcinoma is rare and highly aggressive cancer. Surgical resection and adjuvant chemotherapy with SCLC regimen may improve the disease-free survival and overall survival. The accumulation of similar cases will clarify the profile and management of the disease.
Leigh syndrome global patient registry: uniting patients and researchers worldwide
Authors: Zilber Sophia , Woleben Kasey , Johnson Simon C. , de Souza Carolina Fischinger Moura , Boyce Danielle , Freiert Kevin , Boggs Courtney , Messahel Souad , Burnworth Melinda J. , Afolabi Titilola M. , Kayani Saima
Published: September 2023

Background

Leigh Syndrome (LS) is a rare genetic neurometabolic disorder, that leads to the degeneration of the central nervous system and subsequently, early death. LS can be caused by over 80 mutations in mitochondrial or nuclear DNA. Patient registries are important for many reasons, such as studying the natural history of the disease, improving the quality of care, and understanding the healthcare burden. For rare diseases, patient registries are significantly important as patient numbers are small, and funding is limited. Cure Mito Foundation started a global patient registry for LS in September 2021 to identify and learn about the LS patient population, facilitate clinical trial recruitment, and unite international patients and researchers. Priorities were to allow researchers and industry partners to access data at no cost through a clear and transparent process, active patient engagement, and sharing of results back to the community.

Results

Patient registry platform, survey design, data analysis process, and patient recruitment strategies are described. Reported results include demographics, diagnostic information, symptom history, loss of milestones, disease management, healthcare utilization, quality of life, and caregiver burden for 116 participants. Results show a high disease burden, but a relatively short time to diagnosis. Despite the challenges faced by families impacted by Leigh syndrome, participants, in general, are described as having a good quality of life and caregivers are overall resilient, while also reporting a significant amount of stress.

Conclusion

This registry provides a straightforward, no-cost mechanism for data sharing and contacting patients for clinical trials or research participation, which is important given the recruitment challenges for clinical trials for rare diseases. This is the first publication to present results from a global patient registry for Leigh Syndrome, with details on a variety of patient-specific and caregiver outcomes reported for the first time. Additionally, this registry is the first for any mitochondrial disease with nearly 70% of participants residing outside of the United States. Future efforts include continued publication of results and further collaboration with patients, industry partners, and researchers.
HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction
Authors: Zhu Chenxi , Piao Zhehao , Jin Li
Published: September 2023

Background

This study aimed to investigate the role of histone deacetylase 5 (HDAC5) in ventricular remodeling and explore the therapeutic potential of the HDAC5 inhibitor LMK235.

Methods

A transverse aortic constriction (TAC) mouse model and angiotensin II (Ang II)-treated H9C2 cells were used to evaluate the effects of HDAC5 inhibition with LMK235 on ventricular remodeling and cardiac dysfunction. Additionally, the involvement of the extracellular signal-regulated kinase (ERK)/early growth response protein 1 (EGR1) signaling pathway in regulating myocyte enhancer factor 2 A (MEF2A) expression was assessed.

Results

HDAC5 was upregulated in TAC mice and Ang II-treated H9C2 cells, suggesting its involvement in ventricular remodeling and cardiac dysfunction. LMK235 treatment significantly improved cardiac function in TAC mice and attenuated TAC-induced ventricular remodeling and Ang II-induced H9C2 cell hypertrophy. Mechanically, HDAC5 inhibition activated the ERK/EGR1 signaling pathway.

Conclusions

Our findings demonstrate that HDAC5 may suppress the activation of ERK/EGR1 signaling to regulate MEF2A expression and therefore participate in cardiac pathophysiology.
The aftermath of war; mental health, substance use and their correlates with social support and resilience among adolescents in a post-conflict region of Sri Lanka
Authors: Dissanayake Lasith , Jabir Sameeha , Shepherd Thomas , Helliwell Toby , Selvaratnam Lavan , Jayaweera Kaushalya , Abeysinghe Nihal , Mallen Christian , Sumathipala Athula
Published: September 2023

Background

Armed conflicts impact on the health and well-being of everyone, but its effect on adolescent mental health is a significant, yet under-explored area in global health. Mental health disorders which develop during adolescence often lead to behavioural problems, risky decision-making, under-age substance use and can adversely impact on educational attainment. This study aimed to estimate the prevalence of common mental disorders, substance use and their correlates with social support and resilience among adolescents (age 12–19 years) in Vavuniya; a post-conflict region of Sri Lanka.

Methods

A population-based cross-sectional study was conducted, with a modified cluster sampling method used for participant selection. Eight culturally adapted instruments were used for data collection. A total of 585 adolescents participated in the study. Analyses were performed using SPSS Version 23 statistical software package. All statistical tests were two-sided (p < 0.05) and p-values less than 0.05 were considered significant. Chi-square tests were used to explore associations between variables of interest. Spearman rank order correlation was used to examine correlations among depression, hopelessness, quality of life, social support, and resilience.

Results

The mean age of participants was 15.02 (± 2.13) years. Ninety-one (15.6%) participants reported being exposed to one or more war-related events, and 85 (93.4%) participants in this group reported being internally displaced due to war. Fifty-two (8.9%) had dropped out of school and the prevalence of depression (3.9%) and substance use (7%) were low. Correlational analyses revealed that depression and hopelessness were significantly negatively correlated with social support, resilience, and quality of life (p < 0.01). Linear regression analysis suggested that 40% of the variance in resilience of the participants can be explained by perceived social support.

Conclusion

The low prevalence of hopelessness and depression highlights the resilience of this group in the face of adversity. Furthermore, significant negative correlations between hopelessness and depression with perceived social support and resilience suggest that social support and resilience could be protective factors against mental health issues in these adolescents. However, the prevalence of school dropouts calls for a focus on academic attainment to promote better educational outcomes in the adolescents of this conflict-affected region.
Longitudinal Covid-19 effects on child mental health: vulnerability and age dependent trajectories
Authors: Larsen Linda , Schauber Stefan Kilian , Holt Tonje , Helland Maren Sand
Published: September 2023

Background

Few longitudinal studies have investigated the extended long-term impact of the Covid-19 pandemic for children’s and adolescents’ mental health, and a lack of uniform findings suggest heterogeneity in the impact of the pandemic.

Methods

This study investigated child and adolescent mental health symptoms across four occasions (pre-pandemic, initial lockdown, second lockdown, and society post reopening) using data from the Dynamics of Family Conflict study. Child and adolescent depressive vulnerability, age, and sex were explored as trajectory moderators. Children and adolescents (N = 381, Mage = 13.65, SD = 1.74) self-reported their anxiety, depression, and externalizing symptoms. Mixed effects analyses were performed to investigate trajectories across measurement occasions and interaction terms between occasion and moderator variables were included to better understand the heterogeneity in the impact of the pandemic.

Results

Children and adolescents reported increases in anxiety symptoms at the second lockdown (t(523) = −3.66, p < .01) and when society had reopened (t(522) = −4.90, p < .001). An increase in depression symptoms was seen when society had reopened relative to the three previous measurement occasions (ps < 0.01). Depressive vulnerability moderated the trajectory for anxiety symptoms (F(3,498) = 3.05, p = .028), while age moderated the trajectory for depression symptoms (F(3,532) = 2.97, p = .031).

Conclusion

The delayed and negative impact on children’s and adolescents’ mental health underscores the need for continued monitoring, and implementation of support systems to help and mitigate further deterioration.
Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis
Authors: Han Zhitao , Jia Qi , Zhang Jing , Chen Miaomiao , Wang Lining , Tong Kai , He Weiwei , Zhang Yajie , Zhu Weina , Qin Ju , Wang Tao , Liu Tielong , Ma Yong , Chen Yuanming , Zha Siluo , Zhang Chunlei
Published: September 2023

Background

Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events.

Methods

We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets.

Results

It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors.

Conclusion

Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.
ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle
Authors: Yang Hong , Zhen Xiangjin , Yang Yihui , Zhang Yizhi , Zhang Sen , Hao Yue , Du Guanhua , Wang Hongquan , Zhang Bailin , Li Wan , Wang Jinhua
Published: September 2023

Background

Breast cancer (BC) is the leading cause of morbidity and the second leading cause of death among female malignant tumors. Although available drugs have been approved for the corresponding breast cancer subtypes (ER-positive, HER2+) currently, there are still no effective targeted drugs or treatment strategies for metastatic breast cancer or triple-negative breast cancer that lack targets. Therefore, it is urgent to discover new potential targets. ERCC6L is an essential protein involved in chromosome separation during cell mitosis. However, the effect of ERCC6L on the tumorigenesis and progression of breast cancer is unclear.

Methods and results

Here, we found that ERCC6L was highly expressed in breast cancer, especially in TNBC, which was closely related to poor outcomes of patients. An ERCC6L conditional knockout mouse model was first established in this study, and the results confirmed that ERCC6L was required for the development of the mammary gland and the tumorigenesis and progression of mammary gland cancers. In in vitro cell culture, ERCC6L acted as a tumor promoter in the malignant progression of breast cancer cells. Overexpression of ERCC6L promoted cell proliferation, migration and invasion, while knockdown of ERCC6L caused the opposite results. Mechanistically, ERCC6L accelerated the cell cycle by regulating the G2/M checkpoint signalling pathway. Additionally, we demonstrated that there is an interaction between ERCC6L and KIF4A, both of which are closely related factors in mitosis and are involved in the malignant progression of breast cancer.

Conclusions

We first demonstrated that ERCC6L deficiency can significantly inhibit the occurrence and development of mammary gland tumors. ERCC6L was found to accelerate the cell cycle by regulating the p53/p21/CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B signalling pathways, thereby promoting the malignant progression of breast cancer cell lines. There was a direct interaction between KIF4A and ERCC6L, and both are closely associated with mitosis and contribute to growth and metastasis of breast tumor. To sum up, our results suggest that ERCC6L may be used as a promising target for the treatment of BC.