bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of type III dens invaginatus in bilateral immature mandibular central incisors: a case report
Authors: Zhang Jie , Wang Yuan , Xu Lei , Wu Zhifang , Tu Yan
Published: February 2022

Background

Dens invaginatus (DI) is a developmental anomaly, Oehlers Type III DI is the most complex type and early diagnosis and treatment is complicated and challenging. This report presents a rare case of a type IIIb DI associated with a periapical lesion in bilateral immature permanent mandibular central incisors.

Case presentation

An eight-year-old boy referred to our clinic manifesting with pain along with swelling in the mandibular incisors for the past one month. Radiographic examination showed periapical radiolucency exhibiting a scantly defined border, as well as an invagination which had a central invaginated canal extending from the pulp chamber throughout the apical foramen in both mandibular central incisors. We performed two different treatment procedures on the basis of the condition of the main pulp of the mandibular central incisors. in which only the invagination root canal was treated in the right mandibular central incisor, while the invagination and main root canals were treated in the left mandibular central incisor. During the 18-month follow-up period, the teeth were clinically asymptomatic. Imaging examinations indicated complete healing of the periapical lesion and revealed that the wall of the root canal was thickened and the open apex was closed.

Conclusion

For young permanent teeth with type III Dens invaginatus, it is particularly important to keep pulp vitality, which could maintain root development and allow a good long-term prognosis.
COMPANION: development of a patient-centred complexity and casemix classification for adult palliative care patients based on needs and resource use – a protocol for a cross-sectional multi-centre study
Authors: Hodiamont Farina , Schatz Caroline , Gesell Daniela , Leidl Reiner , Boulesteix Anne-Laure , Nauck Friedemann , Wikert Julia , Jansky Maximiliane , Kranz Steven , Bausewein Claudia
Published: February 2022

Background

A casemix classification based on patients’ needs can serve to better describe the patient group in palliative care and thus help to develop adequate future care structures and enable national benchmarking and quality control. However, in Germany, there is no such an evidence-based system to differentiate the complexity of patients’ needs in palliative care. Therefore, the study aims to develop a patient-oriented, nationally applicable complexity and casemix classification for adult palliative care patients in Germany.

Methods

COMPANION is a mixed-methods study with data derived from three subprojects. Subproject 1: Prospective, cross-sectional multi-centre study collecting data on patients’ needs which reflect the complexity of the respective patient situation, as well as data on resources that are required to meet these needs in specialist palliative care units, palliative care advisory teams, and specialist palliative home care. Subproject 2: Qualitative study including the development of a literature-based preliminary list of characteristics, expert interviews, and a focus group to develop a taxonomy for specialist palliative care models. Subproject 3: Multi-centre costing study based on resource data from subproject 1 and data of study centres. Data and results from the three subprojects will inform each other and form the basis for the development of the casemix classification. Ultimately, the casemix classification will be developed by applying Classification and Regression Tree (CART) analyses using patient and complexity data from subproject 1 and patient-related cost data from subproject 3.

Discussion

This is the first multi-centre costing study that integrates the structure and process characteristics of different palliative care settings in Germany with individual patient care. The mixed methods design and variety of included data allow for the development of a casemix classification that reflect on the complexity of the research subject. The consecutive inclusion of all patients cared for in participating study centres within the time of data collection allows for a comprehensive description of palliative care patients and their needs. A limiting factor is that data will be collected at least partly during the COVID-19 pandemic and potential impact of the pandemic on health care and the research topic cannot be excluded.

Trial registration

German Register for Clinical Studies trial registration number: DRKS00020517.
Conceptualising effective symptom management in palliative care: a novel model derived from qualitative data
Authors: Chapman Emma J. , Pini Simon , Edwards Zoe , Elmokhallalati Yousuf , Murtagh Fliss E. M. , Bennett Michael I.
Published: February 2022

Background

Pain, breathlessness and fatigue are some of the most challenging symptoms to manage in patients with advanced disease. Specialist palliative care leads to better symptom management, but factors contributing to successful symptom management in this context have not been explored. Our aim was to understand what facilitates effective symptom management in specialist palliative care within UK hospices and investigate what barriers are experienced.

Methods

This was a grounded theory study using qualitative semi-structured focus groups and interviews. Participants were recruited from multidisciplinary specialist palliative care teams (doctors, nurses, healthcare assistants, physiotherapists, occupational therapists, complementary therapists, social workers and chaplains) working in inpatient, outpatient and community services provided by five hospices in the United Kingdom.

Results

We present a novel qualitative data-derived model of effective symptom management in specialist palliative care. We describe a co-ordinated, multi-faceted, sequential approach involving a process of engagement, partnership, decision-making, and delivery. Interventions to manage symptoms are less effective in psychologically distressed patients. Our data highlights that families of patients have a key role in determining effectiveness of symptom management interventions A holistic approach by a co-ordinated, multi-disciplinary team, including support to recognise and minimise psychological distress might facilitate more effective symptom management. Barriers to symptom management include team discordance and lack of understanding about symptom management by patient and families.

Conclusions

Shared decision-making between patients and professionals and co-ordination of care by a multi-disciplinary team are key components of effective symptom management. Actions to address psychological distress and evaluate the understanding and expectations of patients and their families would enable more effective symptom management. A more effective multi-disciplinary approach would be facilitated by discussion within teams about role competencies and boundaries.
Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: a molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study
Authors: Murad Hussam Aly Sayed , Alqurashi Thamer Mohammed Ahmed , Hussien Mostafa Aly
Published: February 2022

Background

The chemokine CXCL12 and its two receptors (CXCR4 and CXCR7) are involved in inflammation and hematopoietic cell trafficking. This study was designed to investigate molecular docking interactions of four popular cardiovascular-active natural compounds; curcumin, resveratrol, quercetin, and eucalyptol; with these receptors and to predict their drug-like properties. We hypothesize that these compounds can modify CXCL12/CXCR4/CXCR7 pathway offering benefits for coronary artery disease patients.

Methods

Docking analyses were carried and characterized by Molecular Environment (MOE) software. Protein Data Bank (http://www.rcsb.org/) has been retrieved from protein structure generation and crystal structures of CXCR4 and CXCR7 receptors (PDB code = 3ODU and 6K3F). The active sites of these receptors were evaluated and extracted from full protein and molecular docking protocol was done for compounds against them. The presented parameters included docking scores, ligand binding efficiency, and hydrogen bonding. The pharmacokinetic/toxic properties (ADME/T) were calculated using SwissADME, ProTox-II, and Pred-hERG softwares to predict drug-like properties of the compounds. The thermochemical and molecular orbital analysis, and molecular dynamics simulations were also done.

Results

All compounds showed efficient interactions with the CXCR4 and CXCR7 receptors. The docking scores toward proteins 3ODU of CXCR4 and 6K3F of CXCR7 were − 7.71 and − 7.17 for curcumin, − 5.97 and − 6.03 for quercetin, − 5.68 and − 5.49 for trans-resveratrol, and − 4.88 and − 4.70 for (1 s,4 s)-eucalyptol respectively indicating that all compounds, except quercetin, have more interactions with CXCR4 than with CXCR7. The structurally and functionally important residues in the interactive sites of docked CXCR4-complex and CXCR7-complex were identified. The ADME analysis showed that the compounds have drug-like properties. Only (1 s,4 s)-Eucalyptol has potential weak cardiotoxicity. The results of thermochemical and molecular orbital analysis and molecular dynamics simulation validated outcomes of molecular docking study.

Conclusions

Curcumin showed the top binding interaction against active sites of CXCR4 and CXCR7 receptors, with the best safety profile, followed by quercetin, resveratrol, and eucalyptol. All compounds demonstrated drug-like properties. Eucalyptol has promising potential because it can be used by inhalation or skin massage. To our knowledge, this is the first attempt to find binding interactions of these natural agents with CXCR4 and CXCR7 receptors and to predict their druggability.
Job performance in healthcare: a systematic review
Authors: Krijgsheld Marcel , Tummers Lars G. , Scheepers Floortje E.
Published: February 2022

Background

Healthcare organisations face major challenges to keep healthcare accessible and affordable. This requires them to transform and improve their performance. To do so, organisations must influence employee job performance. Therefore, it is necessary to know what the key dimensions of job performance in healthcare are and how these dimensions can be improved. This study has three aims. The first aim is to determine what key dimensions of job performance are discussed in the healthcare literature. The second aim is to determine to which professionals and healthcare organisations these dimensions of job performance pertain. The third aim is to identify factors that organisations can use to affect the dimensions of job performance in healthcare.

Methods

A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The authors searched Scopus, Web of Science, PubMed, and Google Books, which resulted in the identification of 763 records. After screening 92 articles were included.

Results

The dimensions – task, contextual, and adaptative performance and counterproductive work behaviour – are reflected in the literature on job performance in healthcare. Adaptive performance and counterproductive work behaviour appear to be under-researched. The studies were conducted in different healthcare organisations and pertain to a variety of healthcare professionals. Organisations can affect job performance on the macro-, meso-, and micro-level to achieve transformation and improvement.

Conclusion

Based on more than 90 studies published in over 70 journals, the authors conclude that job performance in healthcare can be conceptualised into four dimensions: task, contextual and adaptive performance, and counterproductive work behaviour. Generally, these dimensions correspond with the dimensions discussed in the job performance literature. This implies that these dimensions can be used for further research into job performance in healthcare. Many healthcare studies on job performance focus on two dimensions: task and contextual performance. However, adaptive performance, which is of great importance in constantly changing environments, is under-researched and should be examined further in future research. This also applies to counterproductive work behaviour. To improve job performance, interventions are required on the macro-, meso-, and micro-levels, which relate to governance, leadership, and individual skills and characteristics.
Physician turnover in primary health care services in the East Zone of São Paulo City, Brazil: incidence and associated factors
Authors: Bourget Monique M. M. , Cassenote Alex J. F. , Scheffer Mário C.
Published: February 2022

Background

The shortage and high turnover of physicians is a recurrent problem in health care systems; this is especially harmful to the expansion and full operation of primary health care (PHC). The aim of this paper is to analyze incidence and associated factors with physician turnover in primary health care services in the East Zone of São Paulo City.

Methods

This is a retrospective cohort study of 1378 physicians over a 15 years’ time period based on physicians’ administrative records from two distinct secondary databases. Physicians’ individual characteristics were analyzed including graduation and specialization. Survival analysis techniques such Kaplan-Meier and Cox Regression were used to analyze the termination of contract.

Results

One thousand three hundred seventy-eight physicians were included in the study of which 130 [9.4%(CI95 8.0–11.1%)] remained in the PHC services. The mean and median time until the occurrence of the physician leaving the service was 2.14 years (CI95% 1.98–2.29 years) and 1.17 years [(CI95% 1.05–1.28 years)]. The probability of contract interruption was 45% in the first year and 68% in the second year. Independent factors associated with TEC were identified: workload of 40 h/week HR = 1.71 [(CI95% 1.4–2.09), p < 0.001]; initial salary ≤1052 BGI HR = 1.87 [(CI95 1.64–2.15), p < 0.001]; time since graduation ≤2 years HR =1.36 [(CI95 1.18–1.56), p < 0.001]; and the conclusion of residency in up to 3 years after leaving the service HR = 1.69 [(CI95 1.40–2.04), p < 0.001].

Conclusions

The time of employment of the physician in PHC was relatively short, with a high probability of TEC in the first year. Modifiable factors such as working hours, starting salary, time since graduation from medical school and need to enter in a residency program were associated with TEC. In pointing out that modifiable factors are responsible for long term employment or the end of contract of physicians in PHC services of the Unified Health System in the periphery of a metropolitan area, the study provides support for the planning, implementation and management of policies and strategies aimed at attracting and retaining physicians in suburban, priority or underserved regions.
A qualitative study on promoting reablement among older people living at home in Norway: opportunities and constraints
Authors: Ambugo Eliva Atieno , Dar Imran , Bikova Mariya S. , Førland Oddvar , Tjerbo Trond
Published: February 2022

Background

Healthcare services that traditionally have been provided in long-term care institutions in Norway are increasingly being delivered at home to a growing population of older people with chronic conditions and functional limitations. Fostering reablement among older people is therefore important if they are to live safety at home for as long as possible. This study examines how healthcare professionals and managers (staff) in Norwegian municipalities promote reablement among community-dwelling older people.

Methods

Face-to-face, semi-structured interviews lasting between 21 and 89 min were conducted between November 2018 and March 2019 with healthcare managers (N = 8) and professionals (N = 8 focus groups with 2–5 participants) in six municipalities in Norway. All interviews were audio-recorded, transcribed, and thematically coded inductively and analyzed with the aid of NVivo 12 software.

Results

Overall, healthcare staff in this study used several strategies to promote reablement, including: carrying out assessments to evaluate older people’s functional status and needs (including for safe home environments), and to identify older people’s wishes and priorities with regard to reablement training. Staff designed care plans informed by the needs assessments, and worked with older people on reablement training at a suitable pace. They promoted among older people and staff (within and across care-units) the principle of ‘showing/doing with’ versus ‘doing for’ the older person so as to not enable disablement. Additionally, they supported older people in the safe and responsible use of welfare technology and equipment. Even so, staff also reported constraints to their efforts to foster reablement, such as: heavy workload, high turnover, insufficient training in reablement care, and poor collaboration across care-units.

Conclusion

Older people may be supported to live safely at home by meeting them as individuals with agency, identifying and tailoring services to their needs and wishes, and encouraging their functional abilities by ‘showing/doing with’ versus ‘doing for them’ when possible. The healthcare professionals and managers in this study were positive towards reablement care. However, meeting the resource demands of reablement care is a key challenge.
Trend and projection of skilled birth attendants and institutional delivery coverage for adolescents in 54 low- and middle-income countries, 2000–2030
Authors: Rahman Md. Mizanur , Taniguchi Hiroko , Nsashiyi Raïssa Shiyghan , Islam Rashedul , Mahmud Syed Riaz , Rahman Shafiur , Jung Jenny , Khan Shahjahan
Published: February 2022

Background

Limitations to accessing delivery care services increase the risks of adverse outcomes during pregnancy and delivery for all pregnant women, particularly among adolescents in LMICs. In order to inform adolescent-specific delivery care initiatives and coverage, we conducted a comprehensive analysis of trends, projections and inequalities in coverage of delivery care services among adolescents at national, urban-rural and socio-economic levels in LMICs.

Methods

Using 224 nationally representative cross-sectional survey data between 2000 and 2019, we estimated the coverage of institutional delivery (INSD) and skilled birth attendants (SBA). Bayesian hierarchical regression models were used to estimate trends, projections and determinants of INSD and SBA.

Results

Coverage of delivery care services among adolescents increased substantially at the national level, as well as in both urban and rural areas in most countries between 2000 and 2018. Of the 54 LMICs, 24 countries reached 80% coverage of both INSD and SBA in 2018, and predictions for 40 countries are set to exceed 80% by 2030. The trends in coverage of INSD and SBA of adult mothers mostly align with those for adolescent mothers. Our findings show that urban-rural and wealth-based inequalities to delivery care remain persistent by 2030. In 2018, urban settings across 54 countries had higher rates of coverage exceeding 80% compared to rural for both INSD (45 urban, 16 rural) and SBA (50 urban, 19 rural). Several factors such as household head age ≥ 46 years, household head being female, access to mass media, lower parity, higher education, higher ANC visits and higher socio-economic status could increase the coverage of INSD and SBA among adolescents and adult women.

Conclusions

More than three-quarters of the LMICs are predicted to achieve 80% coverage of INSD and SBA among adolescent mothers in 2030, although with sustained inequalities.
Seroprevalence of brucellosis, Q fever and Rift Valley fever in domestic ruminants in Guinea in 2017–2019
Authors: Troupin Cécile , Ellis Isabelle , Doukouré Bakary , Camara Alimou , Keita Moustapha , Kagbadouno Moise , Bart Jean-Mathieu , Diallo Ramadan , Lacôte Sandra , Marianneau Philippe , Groschup Martin H , Tordo Noël
Published: February 2022

Background

Brucellosis, Q fever and Rift Valley fever are considered as Neglected Zoonotic Diseases (NZDs) leading to socioeconomic losses in livestock globally, and particularly in developing countries of Africa where they are under-reported. In this study, we evaluated the seroprevalence of these 3 zoonotic diseases in domestic ruminants in Guinea from 2017 to 2019. A total of 1357 sera, sampled from 463 cattle, 408 goats and 486 sheep, were collected in 17 Guinean prefectures and analyzed by enzyme-linked immunosorbent assay (ELISA).

Results

Cattle was the species with highest seroprevalence (5 to 20-fold higher than in small ruminants) for the three diseases. The seroprevalence of brucellosis, mostly focused in Western Guinea, was 11.0% (51 of 463) in cattle, 0.4% (2 in 486) in sheep while no specific antibodies were found in goats. Q fever, widespread across the country, was the most frequently detected zoonosis with a mean seroprevalence of 20.5% (95 in 463), 4.4% (18 in 408) and 2.3% (11 in 486) in cattle, goats and sheep, respectively. The mean seroprevalence of RVF was 16.4% (76 in 463) in cattle, 1.0% (4 in 408) in goats and 1.0% (5 in 486) in sheep. Among the samples 19.3% were seropositive for at least one of the three NZDs, 2.5% showed specific antibodies against at least two pathogens and 4 cattle (0.8%) were seropositive for all three pathogens. In cattle, adults over 3-years old and females presented a higher antibody seroprevalence for the three diseases, in congruence with putative exposure risk.

Conclusions

This study confirms the circulation of these three zoonotic pathogens in Guinea and highlights the need for implementing a syndromic surveillance of ruminant abortions by the Guinean veterinary authorities as well as for the screening of the human population at risk (veterinarians, breeders, slaughterers) in a One Health perspective.
Validation and reproducibility of a semi-qualitative food frequency questionnaire for assessment of sodium intake in Iranian population
Authors: Mohammadifard Noushin , Grau Narges , Khosravi Alireza , Esmaillzadeh Ahmad , Feizi Awat , Abdollahi Zahra , Sarrafzadegan Nizal
Published: February 2022

Background

Few semi-quantitative food frequency questionnaires (SFFQ)s has yet been developed to assess sodium intake in Middle East region. This study was performed to validate a SFFQ for assessment of sodium consumption and food groups΄ contribution to sodium intake.

Methods

This study was performed on 219 healthy participants including 113 adults aged ≥19 years and 106 children aged 6–18 years in Isfahan, Iran. They were administered two SFFQ at the beginning and after 1 year to evaluate the reproducibility. The validity of SFFQ for assessment of sodium intake was compared with 24-h urine sodium and twelve 24-h dietary recalls which were completed monthly during a year as two standard methods.

Results

Correlation coefficient between the contribution of food groups to sodium intake based on SFFQ and 24-h dietary recalls varied from 0.04 for legumes (P = 0.667) to 0.47 for added salt (P < 0.001). There was a significant correlation between the estimated total sodium intake based on SFFQ and both standard methods (P < 0.01). Intraclass correlation coefficient (95% CI) between first and second SFFQ had a diverse range from 0.10 (-0.05, 0.17) for fats and oils to 0.49 (0.28, 0.69) for bread. According to the Bland-Altman plots, we observed an acceptable level of agreement between the two methods for sodium intake.

Conclusions

The SFFQ was a relatively valid and reproducible method for estimating sodium intake. Combination of this SFFQ with a valid prediction of 24-h urinary sodium excretion can be useful in achieving more accurate results.
The oxygenation module: the missing link in using sleep apnea devices to treat COVID-19 pneumonia at home
Authors: Bliznuks Dmitrijs , Kistkins Svjatoslavs , Teličko Jevgēnijs , Geža Vadims , Zāģeris Ģirts , Svaža Artis , Syundyukov Emil , Purenkovs Mārtiņš , Zeme Dana , Jēkabsone Solveiga , Žentiņa Dace , Pīrāgs Valdis , Taivans Immanuels
Published: February 2022

Background

The study aims at solving the problem with the limitations of the homecare CPAP equipment such as sleep apnea devices in the treatment of COVID-19 pneumonia. By adding an advanced, rapid-to-produce oxygenation module to existing CPAP devices we allow distributing healthcare at all levels, reducing the load on intensive care units, promoting treatment in the early stages at homecare. A significant part of the COVID-19 pneumonia patients requires not only an oxygen supply but also additional air pressure. Existing home care devices are able to create precise positive airway pressure, but cannot precisely measure supplied oxygen concentration. Either uses uncertified and potentially unsafe mechanisms.

Results

The developed system allows using certified and widely available CPAP (constant positive airway pressure) devices to perform the critical function of delivering pressure and oxygen to airways. CPAP device is connected to the designed add-on module that can provide predefined oxygen concentration in a precise and stable manner. Clinical test results include data from 12 COVID-19 positive patients. The device has been compared against certified NIV (non-invasive) equipment under 6–20 hPa pressure and 30–70% FiO2. Tests have proved that the developed system can achieve the same SaO2 (p = 0.93) and PaO2 (p = 0.80) levels as NIV with clinically insignificant differences. Test results show that the designed system can substitute NIV equipment for a significant part of COVID-19 patients while leaving existing NIV devices for unstable and critical patients. The system has been designed to be mass-produced while having medically certified critical components.

Conclusion

The clinical testing of the new device for oxygen supplementation of patients treated using simple CPAP devices looks promising and could be used for the treatment of COVID-19 pneumonia.
Experience of danaparoid to treat vaccine-induced immune thrombocytopenia and thrombosis, VITT
Authors: Myllylahti Lasse , Pitkänen Hanna , Magnani Harry , Lassila Riitta
Published: February 2022

Background

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and may cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management. Danaparoid has good efficacy and safety in treatment of heparin-induced thrombocytopenia. We report here our experience of the administration and monitoring danaparoid in VITT.

Methods

We diagnosed a series of six hospitalized cases of VITT, based on the international diagnostic guidance. All VITT-related data were from the local electronic medical and laboratory record system and were analyzed with IBM SPSS Statistics.

Results

Predominately women in their late 40’s developed VITT on average 24 days (range 9–59) after the first ChAdOx1 dose. Clinical presentation included single or multiple venous and/or arterial thrombosis, moderate thrombocytopenia and high D-dimer levels. After detecting PF4 antibodies subcutaneous danaparoid was our first-line antithrombotic treatment with an average duration of three weeks. The median plasma anti-FXa activity was in the lower part of the therapeutic range and during the first week of danaparoid administration clinical symptoms, platelet counts, and fibrin turnover resolved or significantly improved. The average duration of hospital admission was 10 days [2–18]. One patient died but the other five patients recovered completely.

Conclusions

The clinical outcomes of our small cohort align with the earlier published reports, and support danaparoid as a rational option for the initial anticoagulation of VITT patients.
Analysis of the COVID-19 pandemic: lessons towards a more effective response to public health emergencies
Authors: Assefa Yibeltal , Gilks Charles F. , Reid Simon , van de Pas Remco , Gete Dereje Gedle , Van Damme Wim
Published: February 2022

Background

The pandemic of Coronavirus Disease 2019 (COVID-19) is a timely reminder of the nature and impact of Public Health Emergencies of International Concern. As of 12 January 2022, there were over 314 million cases and over 5.5 million deaths notified since the start of the pandemic. The COVID-19 pandemic takes variable shapes and forms, in terms of cases and deaths, in different regions and countries of the world. The objective of this study is to analyse the variable expression of COVID-19 pandemic so that lessons can be learned towards an effective public health emergency response.

Methods

We conducted a mixed-methods study to understand the heterogeneity of cases and deaths due to the COVID-19 pandemic. Correlation analysis and scatter plot were employed for the quantitative data. We used Spearman’s correlation analysis to determine relationship strength between cases and deaths and socio-economic and health systems. We organized qualitative information from the literature and conducted a thematic analysis to recognize patterns of cases and deaths and explain the findings from the quantitative data.

Results

We have found that regions and countries with high human development index have higher cases and deaths per million population due to COVID-19. This is due to international connectedness and mobility of their population related to trade and tourism, and their vulnerability related to older populations and higher rates of non-communicable diseases. We have also identified that the burden of the pandemic is also variable among high- and middle-income countries due to differences in the governance of the pandemic, fragmentation of health systems, and socio-economic inequities.

Conclusion

The COVID-19 pandemic demonstrates that every country remains vulnerable to public health emergencies. The aspiration towards a healthier and safer society requires that countries develop and implement a coherent and context-specific national strategy, improve governance of public health emergencies, build the capacity of their (public) health systems, minimize fragmentation, and tackle upstream structural issues, including socio-economic inequities. This is possible through a primary health care approach, which ensures provision of universal and equitable promotive, preventive and curative services, through whole-of-government and whole-of-society approaches.
Alcohol outlets and alcohol consumption in changing environments: prevalence and changes over time
Authors: Auchincloss Amy H. , Niamatullah Saima , Adams Maura , Melly Steven J. , Li Jingjing , Lazo Mariana
Published: February 2022

Background

To examine whether changes in density of neighborhood alcohol outlets affected changes in alcohol consumption 1-year after regulatory changes increased alcohol availability.

Methods

Person-level data came from a population-based cohort (aged 21–64) residing in/around the Philadelphia, Pennsylvania metropolitan area (2016–2018, N = 772). Fifty-eight percent lived in a state that began implementing new regulations (Pennsylvania) and the remainder lived in states without major regulatory changes (Delaware and New Jersey). Alcohol consumption was assessed as days per week (pw), drinks pw, high consumption (≥8 drinks pw), and binge drinking. Availability of off-premise alcohol outlets was assessed using 1-mile density and distance. Regression models adjusted for age, gender, race/ethnicity, income, education, health status, state and population density.

Results

Cross-sectional analyses found that higher outlet density was associated with more alcohol consumption (days, drinks, high consumption; all p < 0.03) and residing farther from an outlet was associated with less alcohol consumption (days and drinks; all p < 0.04). In longitudinal analyses, relative to no change in outlets, exposure to more outlets was associated with 64% higher odds of drinking on more days pw (p < 0.049) and 55% higher odds of consuming more drinks pw (p < 0.081). However, the longitudinal association between changes in outlets and changes in consumption did not differ for residents in Pennsylvania vs. nearby states. In cross-sectional and longitudinal analyses, outlets were not related to binge drinking.

Conclusion

Off-premise outlets were associated with alcohol consumption consistently in cross-sectional analysis and in some longitudinal analyses. Results can inform future studies that wish to evaluate longer-term changes in increased alcohol availability and effects on consumption.
Cost, cost-consequence and cost-effectiveness evaluation of a practice change intervention to increase routine provision of antenatal care addressing maternal alcohol consumption
Authors: Szewczyk Zoe , Reeves Penny , Kingsland Melanie , Doherty Emma , Elliott Elizabeth , Wolfenden Luke , Tsang Tracey W. , Dunlop Adrian , Searles Andrew , Wiggers John
Published: February 2022

Background

Implementation of antenatal clinical guideline recommendations for addressing maternal alcohol consumption is sub-optimal. There is a complete absence of evidence of the cost and cost-effectiveness of delivering practice change interventions addressing maternal alcohol consumption amongst women accessing maternity services. The study sought to determine the cost, cost-consequence and cost-effectiveness of developing and delivering a multi-strategy practice change intervention in three sectors of a health district in New South Wales, Australia.

Methods

The trial-based economic analyses compared the costs and outcomes of the intervention to usual care over the 35-month period of the stepped-wedge trial. A health service provider perspective was selected to focus on the cost of delivering the practice change intervention, rather than the cost of delivering antenatal care itself. All costs are reported in Australian dollars ($AUD, 2019). Univariate and probabilistic sensitivity analyses assessed the effect of variation in intervention effect and costs.

Results

The total cost of delivering the practice change intervention across all three sectors was $367,646, of which $40,871 (11%) were development costs and $326,774 (89%) were delivery costs. Labour costs comprised 70% of the total intervention delivery cost. A single practice change strategy, ‘educational meetings and educational materials’ contributed 65% of the delivery cost. Based on the trial’s primary efficacy outcome, the incremental cost effectiveness ratio was calculated to be $32,570 (95% CI: $32,566–$36,340) per percent increase in receipt of guideline recommended care. Based on the number of women attending the maternity services during the trial period, the average incremental cost per woman who received all guideline elements was $591 (Range: $329 - $940) . The average cost of the intervention per eligible clinician was $993 (Range: $640-$1928).

Conclusion

The intervention was more effective than usual care, at an increased cost. Healthcare funders’ willingness to pay for this incremental effect is unknown. However, the strategic investment in systems change is expected to improve the efficiency of the practice change intervention over time. Given the positive trial findings, further research and monitoring is required to assess the sustainability of intervention effectiveness and whether economies of scale, or reduced costs of intervention delivery can be achieved without impact on outcomes.

Trial registration

The trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017).
Transfer of knowledge to diagnose infant abuse and its incidence – a time-series analysis from Sweden
Authors: Högberg Ulf
Published: February 2022

Aim

To analyse the transfer of knowledge on how to detect physical abuse, especially shaken baby syndrome/abusive head trauma (SBS/AHT), and its association to trends in infant abuse diagnoses (maltreatment and assault).

Methods

Design: retrospective population-based and quasi-experimental. Setting: Sweden 1987–2019. Patients: Children below age 1 year, selected from the National Patient Register (n = 1150). Exposures: Literature search for transfer of knowledge by diffusion, dissemination and implementation, and whether supportive or disruptive of the SBS/AHT paradigm. Main outcome measure: Abuse diagnoses (maltreatment or assault). Analyses: Incidence rate, incidence rate ratio (IRR).

Results

The overall incidence rate of abuse was 32.23 per 100,000 during the years 1987–2019. It was rather stable 1987–2000. The SBS diagnosis was introduced in the late 1990s. A comprehensive increase of transfer of knowledge on physical abuse, specifically on SBS/AHT and dangers of shaking, took place from 2002 and onward through diffusion, dissemination and implementation. Maltreatment diagnoses, but not assault diagnosis, increased steeply during 2002–2007, peaking in 2008–2013 [IRR 1.63 (95% confidence interval 1.34–1.98)]. Transfer of disruptive knowledge on SBS/AHT during the period 2014–2019 was associated with a decline in maltreatment diagnoses [IRR 0.84 (95% confidence interval 0.71–0.99)].

Conclusion

An increase in maltreatment diagnoses was associated with transfer of supportive knowledge of the SBS/AHT paradigm, while a decline occurred toward the end of the study period, which might indicate a burgeoning de-implementation process.
Differential regulation of progranulin derived granulin peptides
Authors: Zhang Tingting , Du Huan , Santos Mariela Nunez , Wu Xiaochun , Pagan Mitchell D. , Trigiani Lianne Jillian , Nishimura Nozomi , Reinheckel Thomas , Hu Fenghua
Published: February 2022

Background

Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). PGRN is comprised of 7.5 granulin repeats and is processed into individual granulin peptides in the lysosome. However, very little is known about the levels and regulations of individual granulin peptides due to the lack of specific antibodies.

Results

Here we report the generation and characterization of antibodies specific to each granulin peptide. We found that the levels of granulins C, E and F are regulated differently  compared to granulins A and B in various tissues. The levels of PGRN and granulin peptides vary in different brain regions and the ratio between granulins and PGRN is highest in the cortical region in the adult male mouse brain. Granulin-A is localized in the lysosome in both neurons and microglia and its levels in microglia increase under pathological conditions. Interestingly,  the levels of granulin A in microglia change correspondingly with PGRN in response to stroke but not demyelination. Furthermore, deficiency of lysosomal proteases and the PGRN binding partner prosaposin leads to alterations in the ratios between individual granulin peptides. Granulins B, C and E are heavily glycosylated and the glycosylation patterns can be regulated.

Conclusion

Our results support that the levels of individual granulin peptides are differentially regulated under physiological and pathological conditions and provide novel insights into how granulin peptides function in the lysosome.
Retraction Note: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4
Authors: Wang Shaowei , Li Boyang , Solomon Victoria , Fonteh Alfred , Rapoport Stanley I. , Bennett David A. , Arvanitakis Zoe , Chui Helena C. , Miller Carol , Sullivan Patrick M. , Wang Hoau-Yan , Yassine Hussein N.
Published: February 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13024-021-00438-3.
Anticancer and antibacterial potentials induced post short-term exposure to electromagnetic field and silver nanoparticles and related pathological and genetic alterations: in vitro study
Authors: Mohamed Aly Fahmy , Nasr Mohamed , Amer Mohamed E. , Abuamara Tamer M. M. , Abd-Elhay Wagih M. , Kaabo Hassan Fathy , Matar Emad Eldin R. , El Moselhy Laila E. , Gomah Tamer Albasyoni , Deban Mohammed Abd EL-Fatah , Shebl Rania Ibrahim
Published: February 2022

Background

Resistance to antibiotics and anticancer therapy is a serious global health threat particularly in immunosuppressed cancer patients. Current study aimed to estimate the antibacterial and anticancer potentials of short-term exposure to extremely low frequency electromagnetic field (ELF-EMF) and silver nanoparticles (AgNPs) either in sole or combined form.

Methods

Antibacterial activity was evaluated via determination of the bacterial viable count reduction percentage following exposure, whereas their ability to induce apoptosis in breast cancer (MCF-7) cell line was detected using annexin V-fluorescein isothiocyanate and cell cycle analysis. Also, oxidative stress potential and molecular profile were investigated.

Results

ELF-EMF and AgNPs significantly (p < 0.01) reduced K. pneumonia viable count of compared to that of S. aureus in a time dependent manner till reaching 100% inhibition when ELF-EMF was applied in combination to 10 µM/ml AgNPs for 2 h. Apoptosis induction was obvious following exposure to either ELF-EMF or AgNPs, however their apoptotic potential was intensified when applied in combination recording significantly (p < 0.001) induced apoptosis as indicated by elevated level of MCF-7 cells in the Pre G1 phase compared to control. S phase arrest and accumulation of cells in G2/M phase was observed following exposure to AgNPs and EMF, respectively. Up-regulation in the expression level of p53, iNOS and NF-kB genes as well as down-regulation of Bcl-2 and miRNA-125b genes were detected post treatment.

Conclusions

The antibacterial and anticancer potentials of these agents might be related to their ability to induce oxidative stress, suggesting their potentials as novel candidates for controlling infections and triggering cancer cells towards self-destruction.
Identification of a novel gene signature predicting response to first-line chemotherapy in BRCA wild-type high-grade serous ovarian cancer patients
Authors: Buttarelli Marianna , Ciucci Alessandra , Palluzzi Fernando , Raspaglio Giuseppina , Marchetti Claudia , Perrone Emanuele , Minucci Angelo , Giacò Luciano , Fagotti Anna , Scambia Giovanni , Gallo Daniela
Published: February 2022

Background

High-grade serous ovarian cancer (HGSOC) has poor survival rates due to a combination of diagnosis at advanced stage and disease recurrence as a result of chemotherapy resistance. In BRCA1 (Breast Cancer gene 1) - or BRCA2-wild type (BRCAwt) HGSOC patients, resistance and progressive disease occur earlier and more often than in mutated BRCA. Identification of biomarkers helpful in predicting response to first-line chemotherapy is a challenge to improve BRCAwt HGSOC management.

Methods

To identify a gene signature that can predict response to first-line chemotherapy, pre-treatment tumor biopsies from a restricted cohort of BRCAwt HGSOC patients were profiled by RNA sequencing (RNA-Seq) technology. Patients were sub-grouped according to platinum-free interval (PFI), into sensitive (PFI > 12 months) and resistant (PFI < 6 months). The gene panel identified by RNA-seq analysis was then tested by high-throughput quantitative real-time PCR (HT RT-qPCR) in a validation cohort, and statistical/bioinformatic methods were used to identify eligible markers and to explore the relevant pathway/gene network enrichments of the identified gene set. Finally, a panel of primary HGSOC cell lines was exploited to uncover cell-autonomous mechanisms of resistance.

Results

RNA-seq identified a 42-gene panel discriminating sensitive and resistant BRCAwt HGSOC patients and pathway analysis pointed to the immune system as a possible driver of chemotherapy response. From the extended cohort analysis of the 42 DEGs (differentially expressed genes), a statistical approach combined with the random forest classifier model generated a ten-gene signature predictive of response to first-line chemotherapy. The ten-gene signature included: CKB (Creatine kinase B), CTNNBL1 (Catenin, beta like 1), GNG11 (G protein subunit gamma 11), IGFBP7 (Insulin-like growth factor-binding protein 7), PLCG2 (Phospholipase C, gamma 2), RNF24 (Ring finger protein 24), SLC15A3 (Solute carrier family 15 member 3), TSPAN31 (Tetraspanin 31), TTI1 (TELO2 interacting protein 1) and UQCC1 (Ubiquinol-cytochrome c reductase complex assembly factor). Cytotoxicity assays, combined with gene-expression analysis in primary HGSOC cell lines, allowed to define CTNNBL1, RNF24, and TTI1 as cell-autonomous contributors to tumor resistance.

Conclusions

Using machine-learning techniques we have identified a gene signature that could predict response to first-line chemotherapy in BRCAwt HGSOC patients, providing a useful tool towards personalized treatment modalities.
Multiple distinct domains of human XIST are required to coordinate gene silencing and subsequent heterochromatin formation
Authors: Dixon-McDougall Thomas , Brown Carolyn J.
Published: February 2022

Background

Mammalian dosage compensation is achieved by the inactivation of one X chromosome in XX individuals. In eutheria this process is initiated early in development by the long non-coding RNA XIST. Studies of the initiation of silencing by XIST have focussed on mouse models, so the domains of XIST required to induce silencing in humans, and their relationship with domains required to establish heterochromatin remain to be determined.

Methods

We have previously established an inducible XIST cDNA in somatic cells and shown it can induce silencing and recruit heterochromatic features. We now assess a series of deletions across the transgene for the ability to induce silencing and integrate these results with time-course and chromatin-remodelling inhibitor treatments to follow the steps of XIST-induced silencing and heterochromatinization.

Discussion

We find that in addition to the previously reported necessity of the 5’ A repeat region for XIST-induced silencing, the 1 kb around the small F repeat region and a non-repetitive region at the 3’ end of the RNA are also required to silence genes. Silencing of genes up to 17 Mb from the XIST integration occurs within 2 days, while formation of a Cot-1 depleted domain is slower, and more dependent on the region encompassing Repeat F. The role of this region encompassing Repeat F in both the silencing of actively transcribed genes, the spread of H3K27me3 and the formation of a transcriptionally inert domain suggests a role in a pathway crucial for the spread of XIST across the chromatin to target distal regions of inactivation. Histone deacetylation requires only the A repeat region, with HDAC3 inhibition showing limited effect on silencing, but an impact on H3K27me3 recruitment, and as a result the recruitment of MacroH2A. Global HDAC inhibition impacted silencing in both a distance and dose-dependent fashion. The E repeat region was required for CIZ1 and H4K20me1 recruitment as well as H3K27me3; however, these appeared to act relatively independently. The H3K27me3 mark established by PRC2 integrated silencing and many of the heterochromatic features, while the PRC1 mark ubH2A appeared to be downstream of silencing in these human somatic cells.