bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation in primary care for an ageing population: a secondary analysis from a scoping review of rehabilitation delivery models
Authors: Seijas Vanessa , Maritz Roxanne , Mishra Satish , Bernard Renaldo M , Fernandes Patricia , Lorenz Viola , Machado Barbara , Posada Ana María , Lugo-Agudelo Luz Helena , Bickenbach Jerome , Sabariego Carla
Published: January 2024

Background

The world population is ageing rapidly. Rehabilitation is one of the most effective health strategies for improving the health and functioning of older persons. An understanding of the current provision of rehabilitation services in primary care (PC) is needed to optimise access to rehabilitation for an ageing population. The objectives of this scoping review are a) to describe how rehabilitation services are currently offered in PC to older persons, and b) to explore age-related differences in the type of rehabilitation services provided.

Methods

We conducted a secondary analysis of a scoping review examining rehabilitation models for older persons, with a focus on PC. Medline and Embase (2015–2022) were searched to identify studies published in English on rehabilitation services for people aged 50 + . Two authors independently screened records and extracted data using the World Health Organization (WHO)’s operational framework, the Primary Health Care Systems (PRIMASYS) approach and the WHO paper on rehabilitation in PC. Data synthesis included quantitative and qualitative analysis.

Results

We synthesised data from 96 studies, 88.6% conducted in high-income countries (HICs), with 31,956 participants and identified five models for delivering rehabilitation to older persons in PC: community, home, telerehabilitation, outpatient and eldercare. Nurses, physiotherapists, and occupational therapists were the most common providers, with task-shifting reported in 15.6% of studies. The most common interventions were assessment of functioning, rehabilitation coordination, therapeutic exercise, psychological interventions, and self-management education. Environmental adaptations and assistive technology were rarely reported.

Conclusions

We described how rehabilitation services are currently provided in PC and explored age-related differences in the type of rehabilitation services received. PC can play a key role in assessing functioning and coordinating the rehabilitation process and is also well-placed to deliver rehabilitation interventions. By understanding models of rehabilitation service delivery in PC, stakeholders can work towards developing more comprehensive and accessible services that meet the diverse needs of an ageing population. Our findings, which highlight the role of rehabilitation in healthy ageing, are a valuable resource for informing policy, practice and future research in the context of the United Nations Decade of Healthy Ageing, the Rehab2030 initiative and the recently adopted WHA resolution on strengthening rehabilitation in health systems, but the conclusions can only be applied to HICs and more studies are needed that reflect the reality in low- and middle-income countries.
Healthcare provider perspectives on integrating a comprehensive spine care model in an academic health system: a cross-sectional survey
Authors: Burton Wren , Salsbury Stacie A. , Goertz Christine M.
Published: January 2024

Background

Healthcare systems (HCS) are challenged in adopting and sustaining comprehensive approaches to spine care that require coordination and collaboration among multiple service units. The integration of clinicians who provide first line, evidence-based, non-pharmacological therapies further complicates adoption of these care pathways. This cross-sectional study explored clinician perceptions about the integration of guideline-concordant care and optimal spine care workforce requirements within an academic HCS.

Methods

Spine care clinicians from Duke University Health System (DUHS) completed a 26-item online survey via Qualtrics on barriers and facilitators to delivering guideline concordant care for low back pain patients. Data analysis included descriptive statistics and qualitative content analysis.

Results

A total of 27 clinicians (57% response) responded to one or more items on the questionnaire, with 23 completing the majority of questions. Respondents reported that guidelines were implementable within DUHS, but no spine care guideline was used consistently across provider types. Guideline access and integration with electronic records were barriers to use. Respondents (81%) agreed most patients would benefit from non-pharmacological therapies such as physical therapy or chiropractic before receiving specialty referrals. Providers perceived spine patients expected diagnostic imaging (81%) and medication (70%) over non-pharmacological therapies. Providers agreed that receiving imaging (63%) and opioids (59%) benchmarks could be helpful but might not change their ordering practice, even if nudged by best practice advisories. Participants felt that an optimal spine care workforce would require more chiropractors and primary care providers and fewer neurosurgeons and orthopedists. In qualitative responses, respondents emphasized the following barriers to guideline-concordant care implementation: patient expectations, provider confidence with referral pathways, timely access, and the appropriate role of spine surgery.

Conclusions

Spine care clinicians had positive support for current tenets of guideline-concordant spine care for low back pain patients. However, significant barriers to implementation were identified, including mixed opinions about integration of non-pharmacological therapies, referral pathways, and best practices for imaging and opioid use.
Exploring effective implementation pathways to become an excellent chief financial officer in public hospital: a qualitative comparative analysis (QCA) from China
Authors: Wang Hongzhi , Li Junjun , Xiang Xin
Published: January 2024

Background

Hospital chief financial officer (CFO) contributes to improving health system performance. However, how to become an excellent hospital CFO has rarely been considered from a holistic perspective. This paper aims to identify competencies required by hospital CFO to fulfil the position’s responsibilities and explore effective implementation pathways to generate high performance and improve healthcare service.

Methods

We conducted 61 semi-structured interviews with individuals in key leadership positions in China’s hospitals and researchers focusing on healthcare system management to identify core competencies necessary for hospital CFO. Interviews were analysed through a multi-stage review process and modified via expert vetting using a national panel of 23 professors. Subsequently, interviews were conducted with 32 hospital CFOs from 14 provinces throughout September 2021 to May 2022. We scored the performance of 32 hospital CFOs in various aspects of competency and used the fuzzy-set qualitative comparative analysis to explore the competency configurations of excellent CFOs.

Results

We identify seven core competencies necessary for a hospital CFO to fulfil management practices, including personal morality, resource management, strategy management, learning ability, negotiating skill, leadership skill, and financial management. The findings indicate that a single competency factor is not a necessary condition to become an excellent hospital CFO. The results of qualitative comparative analysis then make it possible to propose four configurational paths, namely, supportive, interpersonal, all-around development, and technical, to become an excellent hospital CFO and achieve effective managerial performance.

Conclusions

The responsibilities of hospital CFOs are complex and varied, hence, a better understanding of competencies required by CFO is essential to implement their responsibilities effectively. The identification in this study of the four effective implementation pathways to becoming an excellent hospital CFO enriches the literature on hospital management and provides implications for China’s hospitals and their CFOs.
Geospatial analysis of Plasmodium falciparum serological indicators: school versus community sampling in a low-transmission malaria setting
Authors: Jaramillo-Underwood Alicia , Herman Camelia , Jean Samuel E. , Nace Doug , Elder E. Scott , Robinson Keri , Knipes Alaine , Worrell Caitlin M. , Fox LeAnne M. , Desir Luccene , Fayette Carl , Javel Alain , Monestime Franck , Mace Kimberly E. , Udhayakumar Venkatachalam , Won Kimberly Y. , Chang Michelle A. , Lemoine Jean F. , Rogier Eric
Published: January 2024

Background

Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling.

Methods

This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti.

Results

Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman’s rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09–0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35–0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47–0.49).

Conclusions

In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area.
The quality of care delivered to residents in long-term care in Australia: an indicator-based review of resident records (CareTrack Aged study)
Authors: Hibbert Peter D. , Molloy Charlotte J. , Cameron Ian D. , Gray Leonard C. , Reed Richard L. , Wiles Louise K. , Westbrook Johanna , Arnolda Gaston , Bilton Rebecca , Ash Ruby , Georgiou Andrew , Kitson Alison , Hughes Clifford F. , Gordon Susan J. , Mitchell Rebecca J. , Rapport Frances , Estabrooks Carole , Alexander Gregory L. , Vincent Charles , Edwards Adrian , Carson-Stevens Andrew , Wagner Cordula , McCormack Brendan , Braithwaite Jeffrey
Published: January 2024

Background

This study estimated the prevalence of evidence-based care received by a population-based sample of Australian residents in long-term care (LTC) aged ≥ 65 years in 2021, measured by adherence to clinical practice guideline (CPG) recommendations.

Methods

Sixteen conditions/processes of care amendable to estimating evidence-based care at a population level were identified from prevalence data and CPGs. Candidate recommendations (n = 5609) were extracted from 139 CPGs which were converted to indicators. National experts in each condition rated the indicators via the RAND-UCLA Delphi process. For the 16 conditions, 236 evidence-based care indicators were ratified.

A multi-stage sampling of LTC facilities and residents was undertaken. Trained aged-care nurses then undertook manual structured record reviews of care delivered between 1 March and 31 May 2021 (our record review period) to assess adherence with the indicators.

Results

Care received by 294 residents with 27,585 care encounters in 25 LTC facilities was evaluated. Residents received care for one to thirteen separate clinical conditions/processes of care (median = 10, mean = 9.7). Adherence to evidence-based care indicators was estimated at 53.2% (95% CI: 48.6, 57.7) ranging from a high of 81.3% (95% CI: 75.6, 86.3) for Bladder and Bowel to a low of 12.2% (95% CI: 1.6, 36.8) for Depression. Six conditions (skin integrity, end-of-life care, infection, sleep, medication, and depression) had less than 50% adherence with indicators.

Conclusions

This is the first study of adherence to evidence-based care for people in LTC using multiple conditions and a standardised method. Vulnerable older people are not receiving evidence-based care for many physical problems, nor care to support their mental health nor for end-of-life care. The six conditions in which adherence with indicators was less than 50% could be the focus of improvement efforts.
MPZL2—a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population
Authors: Zhang Lang , Yang Jin-Yuan , Wang Qiu-Quan , Gao Xue , Wang Guo-Jian , Han Ming-Yu , Kang Dong-Yang , Han Dong-Yi , Huang Sha-Sha , Yuan Yong-Yi
Published: January 2024

Background

Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss.

Methods

In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing.

Results

Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency.

Conclusions

We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.
Analysing the six-year malaria trends at Metehara Health Centre in Central Ethiopia: the impact of resurgence on the 2030 elimination goals
Authors: Mandefro Aynalem , Tadele Geletta , Mekonen Bacha , Golassa Lemu
Published: January 2024

Background

Despite Ethiopia’s concerted efforts to eliminate malaria by 2030, the disease continues to pose a significant public health and socioeconomic challenge in the country. The year 2021 witnessed 2.78 million malaria cases and 8041 associated deaths, emphasizing the persistent threat. Monitoring the prevalence trend of malaria is crucial for devising effective control and elimination strategies. This study aims to assess the trend of malaria prevalence at the Metehara Health Centre in the East Shoa Zone, Ethiopia.

Methods

A retrospective study, spanning from February to September 2023, utilized malaria registration laboratory logbooks at Metehara Health Centre to evaluate the prevalence of malaria from 2017/18 to 2022/23. Malaria and related data were collected using a pre-designed data collection sheet. Descriptive statistics were employed for data summarization, presented through graphs and tables.

Results

Out of 59,250 examined blood films, 17.4% confirmed the presence of Plasmodium infections. Among the confirmed cases, 74.3%, 23.8%, and 1.84% were attributed to Plasmodium falciparum, Plasmodium vivax, and mixed infections, respectively. The trend of malaria exhibited a steady decline from 2017/18 to 2021/22, reaching 9.8% prevalence. However, an abrupt increase to 26.5% was observed in 2022/23. Males accounted for a higher proportion (66%) of cases compared to females (34%). The age group 15–24 years experienced the highest malaria incidence at 42%. Notably, malaria cases peaked during autumn (September to November) at 43% and reached the lowest percentage during spring (March to May) at 13%.

Conclusion

Malaria persists as a significant health challenge in and around Metehara, central Ethiopia, predominantly driven by Plasmodium falciparum. The five-year declining trend was interrupted by a notable upsurge in 2022/23, indicating a resurgence of malaria in the study area. It is imperative to adopt a reverse strategy to sustain the progress achieved by the national malaria control plan.
What our children lost and gained at the time of school closure during the Covid-19 pandemic: a study on psychological distress, behavioural concerns and protective factors of resilience among preschool children in Kerala, India
Authors: Vincent Jose , Santhakumari Resmi Madhusoodanan , Nalinakumari Kesavan Nair Anjana , Sharahudeen Anisha , K.P Asvini , Suresh Meenu Maheswari , Valamparampil Mathew J. , A.V Gayathri , Sujatha Chintha , Thekkumkara Surendran Anish
Published: January 2024

Background

The pandemic has put at risk the social and emotional development of children on account of the paucity of arenas for social interaction. This study from Kerala, India was conducted to assess the resilience factors, behavioural concerns, psychological distress symptoms among the children aged 3 to 5 years. We also tried to look into the lost opportunities that could have aided the social and emotional development of children like peer interaction, child care hours.

Methods

The cross-sectional study was conducted among the children aged 3 to 5 years. A total of 535 children attending the immunisation clinics were enrolled by consecutive sampling. Devereux Early Childhood Assessment P2 (DECA P2) questionnaire was used to assess the levels of resilient factors and behavioural concerns in the study population.

Results

We observed a high proportion of children in the area of need category of protective factors under DECA P2. The proportion of children falling under area of concern was 64.5%, 49%, 68.4% for attachment/relationship, self-regulation, and initiative respectively. 24.9% study subjects have a behavioural concern score that puts them in the area of need category. The logistic regression model we created identified ‘Male Gender,’ ‘Mothers could spend only less time for child care’ and ‘electronic devices used as pacifier’ as significant predictors for belonging to Area of need Behavioural Concerns T score category.

Conclusion

A large proportion of children aged between 3 to 5 years with reported behavioural concerns and lack of protective factors for socioemotional development. This can be attributed partly to the ongoing pandemic and its associated restrictions. The increased child care hours invested by parents or grandparents could have sized down the full impact that the pandemic would have had on the socio emotional development of the child. Increased time spent using electronic devices coupled with dwindled opportunities for interaction with peers have been notable challenges.
Time-series analysis of temperature variability and cardiovascular emergency department visits in Atlanta over a 27-year period
Authors: Lane Morgan , Ebelt Stefanie , Wu Zhen , Scovronick Noah , D’Souza Rohan R. , Chang Howard H.
Published: January 2024

Background

Short-term temperature variability, defined as the temperature range occurring within a short time span at a given location, appears to be increasing with climate change. Such variation in temperature may influence acute health outcomes, especially cardiovascular diseases (CVD). Most research on temperature variability has focused on the impact of within-day diurnal temperature range, but temperature variability over a period of a few days may also be health-relevant through its impact on thermoregulation and autonomic cardiac functioning. To address this research gap, this study utilized a database of emergency department (ED) visits for a variety of cardiovascular health outcomes over a 27-year period to investigate the influence of three-day temperature variability on CVD.

Methods

For the period of 1993–2019, we analyzed over 12 million CVD ED visits in Atlanta using a Poisson log-linear model with overdispersion. Temperature variability was defined as the standard deviation of the minimum and maximum temperatures during the current day and the previous two days. We controlled for mean temperature, dew point temperature, long-term time trends, federal holidays, and day of week. We stratified the analysis by age group, season, and decade.

Results

All cardiovascular outcomes assessed, except for hypertension, were positively associated with increasing temperature variability, with the strongest effects observed for stroke and peripheral vascular disease. In stratified analyses, adverse associations with temperature variability were consistently highest in the moderate-temperature season (October and March-May) and in the 65 + age group for all outcomes.

Conclusions

Our results suggest that CVD morbidity is impacted by short-term temperature variability, and that patients aged 65 and older are at increased risk. These effects were more pronounced in the moderate-temperature season and are likely driven by the Spring season in Atlanta. Public health practitioners and patient care providers can use this knowledge to better prepare patients during seasons with high temperature variability or ahead of large shifts in temperature.
The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway
Authors: Karakostis Konstantinos , Malbert-Colas Laurence , Thermou Aikaterini , Vojtesek Borek , Fåhraeus Robin
Published: January 2024

Background

The ATM kinase constitutes a master regulatory hub of DNA damage and activates the p53 response pathway by phosphorylating the MDM2 protein, which develops an affinity for the p53 mRNA secondary structure. Disruption of this interaction prevents the activation of the nascent p53. The link of the MDM2 protein—p53 mRNA interaction with the upstream DNA damage sensor ATM kinase and the role of the p53 mRNA in the DNA damage sensing mechanism, are still highly anticipated.

Methods

The proximity ligation assay (PLA) has been extensively used to reveal the sub-cellular localisation of the protein—mRNA and protein–protein interactions. ELISA and co-immunoprecipitation confirmed the interactions in vitro and in cells.

Results

This study provides a novel mechanism whereby the p53 mRNA interacts with the ATM kinase enzyme and shows that the L22L synonymous mutant, known to alter the secondary structure of the p53 mRNA, prevents the interaction. The relevant mechanistic roles in the DNA Damage Sensing pathway, which is linked to downstream DNA damage response, are explored. Following DNA damage (double-stranded DNA breaks activating ATM), activated MDMX protein competes the ATM—p53 mRNA interaction and prevents the association of the p53 mRNA with NBS1 (MRN complex). These data also reveal the binding domains and the phosphorylation events on ATM that regulate the interaction and the trafficking of the complex to the cytoplasm.

Conclusion

The presented model shows a novel interaction of ATM with the p53 mRNA and describes the link between DNA Damage Sensing with the downstream p53 activation pathways; supporting the rising functional implications of synonymous mutations altering secondary mRNA structures.
Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study
Authors: Kuo Chin-Sung , Kuo Nai-Rong , Yeh Yun-Kai , Lee Yau-Jiunn , Chuang Lee-Ming , Chen Hua-Fen , Chen Ching-Chu , Lee Chun-Chuan , Hsu Chih-Cheng , Li Hung-Yuan , Ou Horng-Yih , Hwu Chii-Min
Published: January 2024

Background

The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.

Methods

Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.

Results

The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.

Conclusion

This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.
Safe inhalation pipe provision (SIPP): protocol for a mixed-method evaluation of an intervention to improve health outcomes and service engagement among people who use crack cocaine in England
Authors: Harris Magdalena , Scott Jenny , Hope Vivian , Busza Joanna , Sweeney Sedona , Preston Andrew , Southwell Mat , Eastwood Niamh , Vuckovic Cedomir , McGaff Caitlynne , Yoon Ian , Wilkins Louise , Ram Shoba , Lord Catherine , Bonnet Philippe , Furlong Peter , Simpson Natasha , Slater Holly , Platt Lucy
Published: January 2024

Background

Over 180,000 people use crack cocaine in England, yet provision of smoking equipment to support safer crack use is prohibited under UK law. Pipes used for crack cocaine smoking are often homemade and/or in short supply, leading to pipe sharing and injuries from use of unsafe materials. This increases risk of viral infection and respiratory harm among a marginalised underserved population. International evaluations suggest crack pipe supply leads to sustained reductions in pipe sharing and use of homemade equipment; increased health risk awareness; improved service access; reduction in injecting and crack-related health problems. In this paper, we introduce the protocol for the NIHR-funded SIPP (Safe inhalation pipe provision) project and discuss implications for impact.

Methods

The SIPP study will develop, implement and evaluate a crack smoking equipment and training intervention to be distributed through peer networks and specialist drug services in England. Study components comprise: (1) peer-network capacity building and co-production; (2) a pre- and post-intervention survey at intervention and non-equivalent control sites; (3) a mixed-method process evaluation; and (4) an economic evaluation. Participant eligibility criteria are use of crack within the past 28 days, with a survey sample of ~ 740 for each impact evaluation survey point and ~ 40 for qualitative process evaluation interviews. Our primary outcome measure is pipe sharing within the past 28 days, with secondary outcomes pertaining to use of homemade pipes, service engagement, injecting practice and acute health harms.

Anticipated impact

SIPP aims to reduce crack use risk practices and associated health harms; including through increasing crack harm reduction awareness among service providers and peers. Implementation has only been possible with local police approvals. Our goal is to generate an evidence base to inform review of the legislation prohibiting crack pipe supply in the UK. This holds potential to transform harm reduction service provision and engagement nationally.

Conclusion

People who smoke crack cocaine in England currently have little reason to engage with harm reduction and drug services. Little is known about this growing population. This study will provide insight into population characteristics, unmet need and the case for legislative reform.

Trial registration: ISRCTN12541454 https://doi.org/10.1186/ISRCTN12541454
Inhibitor of PD-1/PD-L1: a new approach may be beneficial for the treatment of idiopathic pulmonary fibrosis
Authors: Tan Jie , Xue Qianfei , Hu Xiao , Yang Junling
Published: January 2024

Idiopathic pulmonary fibrosis (IPF) is a globally prevalent, progressive disease with limited treatment options and poor prognosis. Because of its irreversible disease progression, IPF affects the quality and length of life of patients and imposes a significant burden on their families and social healthcare services. The use of the antifibrotic drugs pirfenidone and nintedanib can slow the progression of the disease to some extent, but it does not have a reverse effect on the prognosis. The option of lung transplantion is also limited owing to contraindications to transplantation, possible complications after transplantation, and the risk of death. Therefore, the discovery of new, effective treatment methods is an urgent need. Over recent years, various studies have been undertaken to investigate the relationship between interstitial pneumonia and lung cancer, suggesting that some immune checkpoints in IPF are similar to those in tumors. Immune checkpoints are a class of immunosuppressive molecules that are essential for maintaining autoimmune tolerance and regulating the duration and magnitude of immune responses in peripheral tissues. They can prevent normal tissues from being damaged and destroyed by the immune response. While current studies have focused on PD-1/PD-L1 and CTLA-4, PD-1/PD-L1 may be the only effective immune checkpoint IPF treatment. This review discusses the application of PD-1/PD-L1 checkpoint in IPF, with the aim of finding a new direction for IPF treatment.
Causal relationship between gut microbiota and gastrointestinal diseases: a mendelian randomization study
Authors: Wu Kaiwen , Luo Qiang , Liu Ye , Li Aoshuang , Xia Demeng , Sun Xiaobin
Published: January 2024

Background

Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases.

Methods

Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed.

Results

The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results.

Conclusions

The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.
Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study
Authors: Tesser Alessandra , Valencic Erica , Boz Valentina , Tornese Gianluca , Pastore Serena , Zanatta Manuela , Tommasini Alberto
Published: January 2024

Background

H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also features cardiac and endocrine defects, as well as hearing loss, for which the immune pathogenesis appears less clear. Immunomodulatory medications have been shown to improve many symptoms in recent experiences.

Case presentation

A 21-year-old girl was referred to our institute after being diagnosed with H syndrome. Her medical history was characterized by the development of finger and toe deformities, which developed since the first years of life and progressively worsened with clinodactyly. At 6 years of age, she was diagnosed with diabetes mellitus without typical autoantibodies and with bilateral sensorineural hearing loss. She also complained of frequent episodes of lymphadenopathy, sometimes with colliquation and growth retardation due to pancreatic insufficiency. It wasn’t until the genetic diagnosis of H syndrome that the continual increase in acute phase reactants was noticed, suggesting that an immunological pathogenesis may be the source of her problems. During her visit to our institute, she reported serious pain in both feet and hands and difficulty walking due to knee arthritis and muscle contractures. Conventional therapy with steroid injection in affected joints and methotrexate only led to partial improvement. After a thorough assessment of her inflammatory profile showing a high interferon score, the girl received treatment with baricitinib. Furthermore, based on recent data showing that SLC29A3 deficiency results in interferon production because of Toll-like Receptor 7 activation in lysosomes, hydroxychloroquine was also added. The combination of the two drugs resulted for the first time in a rapid and persistent normalization of inflammatory markers, paralleled by a dramatic improvement in symptoms.

Conclusions

We describe the results of inhibiting IFN inflammation in H syndrome and discuss how JAK inhibitors and antimalarials might represent a mechanistically based treatment for this orphan drug disorder.
Synergistic effect of sildenafil combined with controlled hypothermia to alleviate microglial activation after neonatal hypoxia–ischemia in rats
Authors: Julien Pansiot , Zinni Manuela , Bonnel Natacha , El Kamouh Marina , Odorcyk Felipe , Peters Lea , Gautier Emilie-Fleur , Leduc Marjorie , Broussard Cédric , Baud Olivier
Published: January 2024

Background and purpose

The only validated treatment to prevent brain damage associated with hypoxia–ischemia (HI) encephalopathy of the newborn is controlled hypothermia with limited benefits. Additional putative neuroprotective drug candidates include sildenafil citrate, a phosphodiesterase-type 5 inhibitor. The main objective of this preclinical study is to assess its ability to reduce HI-induced neuroinflammation, in particular through its potential effect on microglial activation.

Methods

HI was induced in P10 Sprague–Dawley rats by unilateral carotid permanent artery occlusion and hypoxia (HI) and treated by either hypothermia (HT) alone, Sildenafil (Sild) alone or combined treatment (SildHT). Lesion size and glial activation were analyzed by immunohistochemistry, qRT-PCR, and proteomic analyses performed at P13.

Results

None of the treatments was associated with a significant early reduction in lesion size 72h after HI, despite significant changes in tissue loss distribution. Significant reductions in both Iba1 + (within the ipsilateral hemisphere) and GFAP + cells (within the ipsilateral hippocampus) were observed in SildHT group, but not in the other treatment groups. In microglia-sorted cells, pro-inflammatory markers, i.e. Il1b, Il6, Nos2, and CD86 were significantly downregulated in SildHT treatment group only. These changes were restricted to the ipsilateral hemisphere, were not evidenced in sorted astrocytes, and were not sex dependent. Proteomic analyses in sorted microglia refined the pro-inflammatory effect of HI and confirmed a biologically relevant impact of SildHT on specific molecular pathways including genes related to neutrophilic functions.

Conclusions

Our findings suggest that Sildenafil combined with controlled hypothermia produces maximum effect in mitigating microglial activation induced by HI through complex proteomic regulation. The reduction of neuroinflammation induced by Sildenafil may represent an interesting therapeutic strategy for neonatal neuroprotection.
The HIV-1 gag p6: a promising target for therapeutic intervention
Authors: Chen Xiaowei , Wang Xiao
Published: January 2024

The p6 domain of the Gag precursors (Gag p6) in human immunodeficiency virus type 1 (HIV-1) plays multifunctional roles in the viral life cycle. It utilizes the endosomal sorting complex required for transport (ESCRT) system to facilitate viral budding and release from the plasma membrane through the interactions with the ESCRT-I component tumor susceptibility gene 101 (TSG101) and with the ALG-2 interacting protein X (ALIX). Moreover, Gag p6 contributes to viral replication by a range of posttranslational modifications such as SUMOylation, ubiquitination and phosphorylation. Additionally, Gag p6 also mediates the incorporation of the accessory protein Vpr into virions, thereby promoting Vpr-induced viral replication. However, less attention is focused on Gag p6 as therapeutic intervention. This review focuses on the structures and diverse functions of Gag p6 in viral replication, host cells, and pathogenesis. Additionally, several challenges were also discussed in studying the structure of Gag p6 and its interactions with partners. Consequently, it concludes that the Gag p6 represents an attractive target for the development of antiretroviral drugs, and efforts to develop p6-targeted antiretrovirals are expected to undergo significant growth in the forthcoming years.
The chemokine receptor CCR5: multi-faceted hook for HIV-1
Authors: Faivre Natacha , Verollet Christel , Dumas Fabrice
Published: January 2024

Chemokines are cytokines whose primary role is cellular activation and stimulation of leukocyte migration. They perform their various functions by interacting with G protein-coupled cell surface receptors (GPCRs) and are involved in the regulation of many biological processes such as apoptosis, proliferation, angiogenesis, hematopoiesis or organogenesis. They contribute to the maintenance of the homeostasis of lymphocytes and coordinate the function of the immune system. However, chemokines and their receptors are sometimes hijacked by some pathogens to infect the host organism. For a given chemokine receptor, there is a wide structural, organizational and conformational diversity. In this review, we describe the evidence for structural variety reported for the chemokine receptor CCR5, how this variability can be exploited by HIV-1 to infect its target cells and what therapeutic solutions are currently being developed to overcome this problem.
Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt
Authors: Elnagdy Marwa H. , Magdy Alshimaa , Eldars Waleed , Elgamal Mohamed , El-Nagdy Ahmed Hazem , Salem Omnia , Elmowafy Mohamed Magdy , Elborsh Omar Ahmed , Elshafey Abdelrahman Walid , Kesba Muhammad Magdy , Abdulgalil Ahmed Elsaeed , Sobh Ali
Published: January 2024

Background

Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus’ spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19.

Method

This cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760.

Results

This study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19.

Conclusion

Our study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.
Navigating the challenges of minimally invasive mitral valve surgery: a risk analysis and learning curve evaluation
Authors: Papadopoulos Nestoras , Ntinopoulos Vasileios , Dushaj Stak , Häussler Achim , Odavic Dragan , Biefer Hector Rodríguez Cetina , Dzemali Omer
Published: January 2024

Background

This study aimed to report the risk and learning curve analysis of a minimally invasive mitral valve surgery program performed through a right mini-thoracotomy at a single institution.

Methods

From January 2013 through December 2019, 266 consecutive patients underwent minimally invasive mitral valve surgery in our department and were included in the current study. Multiple logistic regression analysis was used for the adverse event outcome. Distribution over time of perioperative complications, defined as clinical endpoints in the Valve Academic Research Consortium-2 (VARC-2) consensus document, as well as CUSUM charts for assessment of cardiopulmonary bypass and aortic cross-clamping duration over time, has been performed for learning curve assessment.

Results

Overall incidences of postoperative stroke (1.1%), myocardial infarction (1.1%), and thirty-day mortality (1.5%) were low. The mitral valve reconstruction rate in our series was 95%. Multivariable analysis revealed that concomitant tricuspid valve surgery (OR 4.44; 95%CI 1.61–11.80; p = 0.003) was significantly associated with adverse event outcomes. Despite a trend towards adverse event outcomes in patients with preexisting active mitral valve endocarditis (OR 2.69; 95%CI 0.81–7.87; p = 0.082), mitral valve pathology did not significantly impact postoperative morbidity and mortality. Distribution over time of perioperative complications, defined as clinical endpoints in the VARC-2 consensus document, showed a trend towards an improved complication rate after the initial 65–100 procedures.

Conclusions

Mitral valve surgery via right-sided mini-thoracotomy can be implemented safely with low perioperative morbidity and mortality rates. Careful patient selection regarding isolated mitral valve surgery in the presence of degenerative mitral valve disease may represent a significant safety issue during the learning curve.

Trial Registration: The cantonal ethics commission of Zurich approved the study (registration ID 2020-00752, date of approval 24 April 2020).
The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology
Authors: Amoriello Roberta , Memo Christian , Ballerini Laura , Ballerini Clara
Published: January 2024

The central nervous system (CNS) is finely protected by the blood–brain barrier (BBB). Immune soluble factors such as cytokines (CKs) are normally produced in the CNS, contributing to physiological immunosurveillance and homeostatic synaptic scaling. CKs are peptide, pleiotropic molecules involved in a broad range of cellular functions, with a pivotal role in resolving the inflammation and promoting tissue healing. However, pro-inflammatory CKs can exert a detrimental effect in pathological conditions, spreading the damage. In the inflamed CNS, CKs recruit immune cells, stimulate the local production of other inflammatory mediators, and promote synaptic dysfunction. Our understanding of neuroinflammation in humans owes much to the study of multiple sclerosis (MS), the most common autoimmune and demyelinating disease, in which autoreactive T cells migrate from the periphery to the CNS after the encounter with a still unknown antigen. CNS-infiltrating T cells produce pro-inflammatory CKs that aggravate local demyelination and neurodegeneration. This review aims to recapitulate the state of the art about CKs role in the healthy and inflamed CNS, with focus on recent advances bridging the study of adaptive immune system and neurophysiology.