bluuebunny/crossref_metadata_2025 huggingface dataset:
Where is my sample? Investigating pre-analytical pathology sampling errors in a psychiatric hospital
Authors: Scholes-Pearson Emma , Mercadillo Nieves
Published: June 2021

Aims

Errors in the pathology sampling process can be costly for all stakeholders in any clinical setting; however, this process is often overlooked within psychiatry. Over the space of just a few short months at Hollins Park Psychiatric Hospital (HPH) such errors were reported to be numerous with staff raising multiple issues relating to the pathology sampling process. These issues often had a negative impact on patient care, leading to outcomes such as as re-bleeding of patients and delays in interventions. Here, we aim to identify the predominant sources of error in this process and suggest possible improvements to minimise these errors in the future.

Method

Initially, we mapped and analysed each step of the sampling process as it is currently performed in order to identify areas of possible improvement. We then distributed questionnaires to all junior doctors - who are responsible for the handling of samples within the clinical setting – in order to establish error type and frequency. Questions also assessed individual confidence and familiarity with the sampling process.

Result

When mapping the sampling process, we identified all key steps required when sending samples from HPH to Warrington and Halton Hospitals laboratory. This included one pathway for sending routine bloods, and one pathway for urgent bloods. The process for sending routine bloods required more steps and ultimately took longer for samples to reach the laboratory – as expected. Of the issues identified during mapping of the pre-analytical phase, a majority of 77.7% of clinicians reported samples had gone missing or were unreported – with the reasons for this being undetermined in most cases – and 55.5% reported their samples never reached the lab. While on the whole participants were comfortable with the steps involved in sending samples to the laboratory, 77.7% were not aware of the requirement to log samples as they were being sent.

Conclusion

The reasons underlying errors in the sampling process at HPH were multifactorial and included a lack of clinician familiarity with correct procedure, poor sample recording/tracking and lengthy transit times between the patient and laboratory. Here we outline some simple evidence-based recommendations (including education of staff and improved tracking through an electronic requesting system) to help reduce errors and streamline the sampling process in the hopes of improving both efficiency and accuracy, reducing the financial and clinical impact.
Addiction service changes due to COVID-19
Authors: Shahbaz Shumaila , Hashmani Zeeshan , Mayet Soraya
Published: June 2021

Aims

Addictions services had to respond rapidly to reduce COVID-19 transmission to protect patients and staff. Patients with opioid dependence are particularly vulnerable, with high risks. Our community addiction service changed practice in line with COVID-19 guidelines. For patients with opioid dependence; face-to-face contacts were initially reduce and mainly for new starts, restarts and non-attenders. Prescribing changes were completed on an individually risk assessed basis to reduce attendance at the chemist, specifically to reduce transmission, keep patients in treatment and to ensure chemists could continue to function. We document some of the service changes during the COVID-19 lockdown.

Method

Service evaluation had approval from Humber Teaching NHS Foundation Trust. Data retrieved on one Hub of a community addictions service in North England, UK. Patients prescribed opioid substitution treatment for opioid dependence were assessed, with data retrieval through electronic healthcare records. Data were analysed by Microsoft Excel anonymously.

Result

In lockdown (March 2020 to June 2020), we identified 112 patients with opioid dependence prescribed opioid substitution (OST) with methadone or buprenorphine at the Hub. All white British, mean 42 years, most male (75%) and prescribed methadone (78%). Ten were new starts and 8 restarts to OST. Attendance rates did not change: 91% before and 92% during lockdown. Appointment format changed from predominantly face-to-face (92%) to telephone (99%). Most patients (91%;n = 88) were offered take-home naloxone and overdose prevention training of which 14 refused. Supervision days at the chemist for OST reduced significantly from 75% collecting daily at the chemist, reducing to 20% during lockdown. Five patients were shielding and 7 had covid-related symptoms. There was one death during lockdown which was not attributed to covid or overdose.

Conclusion

The addictions service continued to be open and work proactively throughout lockdown, seeing new patients and continuing treatment interventions safely. Major changes were made in line with COVID-19 guidelines, to respond to the threat of transmission. Our service was flexible and able to adapt quickly to remote working. We maintained excellent attendance rates despite changes to the format of consultations. There were no related incidents e.g. overdoses linked to prescribed medications, despite a reduction in supervision, and therefore patients having extra medications. This important finding may be related to the individual risk assessments that we conducted before making changing to prescribing. This was supported by most patients were receiving naloxone to prevent overdoses. Some of the changes, such as telephone consultations, may be beneficial to continue post COVID-19.
An audit of the use of psychotropic medications over the course of admission to a specialist dementia ward
Authors: Singh Sukhmeet , Papworth Margaret , Turrion Concha , Ruhi Shamim
Published: June 2021

Aims

The aim of this audit project was to establish the practices in prescribing and de-prescribing of psychotropic medications for patients on a specialist dementia ward.

Background

There is a great deal of evidence demonstration high rates of polypharmacy, defined as ≥5 drugs, in older adults in general and in those with dementia more specifically. NICE guidelines recommend a structured assessment of a patient with dementia to exclude other potential causes, e.g. pain or delirium. Psychosocial interventions are recommended as first line. Antipsychotics should only be offered second line who present a risk to themselves or others. These should only be used for the shortest time possible and reassessed at least every 6 weeks.

Method

Data were collected for patients (n = 20) discharged from a specialist dementia ward between September 2018 and March 2019. The unit has 14 beds caring for patients with predominantly severe behavioural and psychological symptoms associated with dementia (BPSD). The team is comprised of doctors, nurses, a clinical psychologist, occupational therapists, physiotherapists and pharmacists who meet twice a week to review patients. Data were coded by drug class and counts of medication on admission, at the midpoint and at discharge were conducted. Antipsychotic and benzodiazepine dosages were converted into haloperidol and diazepam equivalence.

Result

Of the 20 patients, 70% were male and 30% female. 95% of the patient (n = 19) were admitted under the Mental Health Act (1983). 20% were managed on 1 to 1 observations and 80% were on 15 min observations. In general, the results show little change in the overall rate of psychotropic prescribing. The mean number of psychotropic medications prescribed per patient on admission was 2.30, at the mid-point of admission it was 2.30 and at discharge it was 2.05. Mean benzodiazepine dosage in diazepam equivalence reduced between admission and discharge from 3.20 mg to 2.10 mg. Mean haloperidol equivalent dosages increased at the midpoint of admission from 1.11 mg to 2.27 mg before reducing to 0.78 mg at discharge.

Conclusion

The results demonstrate minimal change in the overall average number and composition of drugs prescribed. There are differences in the use of regular antipsychotics and benzodiazepines between admission and discharge which are consistent with NICE guidelines. Patients had a structured assessment with regular medicines reconciliation supervised by the team pharmacist. Therefore, the ward environment did allow for detailed discussions about de-prescribing which may not be the case elsewhere.
‘The kind of doctor I wanted to be.’ A qualitative analysis of junior doctors’ reasons for choosing to train in psychiatry and in Wales
Authors: Slater Alan , Saeed Rugi , Fernando Marque , Evans Ceri
Published: June 2021

Aims

To understand the factors underpinning junior doctors’ decision-making processes regarding their choice of psychiatry as a speciality, and why they chose to pursue specialty training in Wales.

Background

Over recent years there have been significant challenges in recruiting junior doctors into psychiatry specialty training, both within the UK and in Wales. To counter this a number of measures have been instituted, including advertising campaigns from the Royal College of Psychiatrists (‘Choose Psychiatry’) and Health Education and Improvement Wales (HEIW) (‘Train Work Live’), together with financial incentives. To date there has been no published evaluation of the effectiveness of these measures.

Method

Two focus groups were run (in August 2019 and January 2020) with trainees appointed to new training posts in August 2019. The focus groups featured set questions acting as prompts for discussion. These focused on various factors behind making decisions to train in Psychiatry and choosing to train within HEIW. The focus groups were recorded and transcribed. Following this a thematic analysis was conducted to identify key elements arising from the discussions.

Result

The focus groups were attended by 14 trainees in total (eleven CT1s, four ST4s.) Living in Wales prior to appointment was the most common factor in leading participants to choose to train in Wales, jointly with having a support network (friends or family) in Wales (each present in 57%, n = 8.) Perceptions around a favourable work-life balance were also important (45%, n = 5.) Interactions with staff in an ambassadorial or support role were a significant driver, especially for international medical graduates. Financial incentives and advertising campaigns appeared to have limited influence over participants’ decision-making, awareness of these being highest among those already working in psychiatry or in Wales.

Having a foundation year job with a psychiatry placement was a common theme in choosing psychiatry as a specialty (43%, n = 6.) Work-life balance of the specialty was also important (21%, n = 3.) Again, after these it was hard to identify coherent themes.

Conclusion

We identified three separate groups, namely CT1s, ST4s and international medical graduates, each with distinct themes underlying a range of needs. There was a broad range of factors underlying trainees’ decisions which should be reflected when planning future recruitment strategies. It appeared that advertising campaigns and financial incentives were of limited influence.
Exploring determinants of self-management in adults with severe mental illness: a qualitative evidence synthesis
Authors: Carswell Claire , Brown Jennifer , Balogun Abisola , Taylor Jo , Coventry Peter , Kitchen Charlotte , Kellar Ian , Peckham Emily , Bellass Sue , Alderson Sarah , Lister Jennie , Holt Richard , Hewitt Catherine , Jacobs Rowena , Shiers David , Boehnke Jan , Ajjan Ramzi , Siddiqi Najma ,   On behalf of the DIAMONDS Research team
Published: June 2021

Aims

To systematically review and synthesise qualitative evidence about determinants of self-management in adults with SMI. The goal is to use findings from this review to inform the design of effective self-management strategies for people with SMI and LTCs.

Background

People living with serious mental illness (SMI) have a reduced life expectancy by around 15–20 years, mainly due to the high prevalence of long-term physical conditions such as diabetes and heart disease. People with SMI face many challenges when trying to manage their physical health. Little is known about the determinants of self-management – managing the emotional and practical issues – of long-term conditions (LTCs) for people with SMI.

Method

Six databases, including CINAHL and MEDLINE, were searched to identify qualitative studies that explored people's perceptions about determinants of self-management in adults with SMI (with or without comorbid LTCs). Self-management was defined according to the American Association of Diabetes Educator's self-care behaviours (AADE7). Determinants were defined according to the Capabilities, Opportunity, Motivations and Behaviours (COM-B) framework. Eligible studies were purposively sampled for synthesis according to the richness of the data (assessed using Ames et al (2017)'s data richness scale), and thematically synthesised.

Result

Twenty-six articles were included in the synthesis. Seven studies focused on self-management of LTCs, with the remaining articles exploring self-management of SMI. Six analytic themes and 28 sub-themes were identified from the synthesis. The themes included: the additional burden of SMI; living with comorbidities; beliefs and attitudes about self-management; support from others for self-management; social and environmental factors; routine, structure and planning. Capabilities for self-management were linked to people's perceptions about the support they received for their SMI and LTC from healthcare professionals, family and friends. Opportunities for self-management were more commonly expressed in the context of social and environmental factors. Motivation for self-management was influenced by beliefs and attitudes, whilst being closely related to the burden of SMI.

Conclusion

The themes identified from the synthesis suggest that capabilities, opportunities and motivations for self-management can be negatively influenced by the experience of SMI, whilst social and professional support, improved access to resources, and increased involvement in care, could promote self-management. Support programmes for people with SMI and LTCs need to account for these experiences and adapt to meet the unique needs of this population.
Handcuff use on forensic psychiatry wards
Authors: Swain Rachel , Klayman Deborah , Reiss David , Buch Kruti , Roberts Sarah
Published: June 2021

Aims

This project aimed to assess the use of handcuffs in a secure forensic mental health hospital.

Background

Handcuffs are used by secure forensic psychiatric wards where patients need to leave the ward and require added restrictive measures for their own or other's safety. The decision to use handcuffs is made by the multi-disciplinary team, with the input of the unit's clinical security team and is assessed based on individual risk and need. This study investigated the frequency, duration and purpose of handcuff use in one secure forensic mental health unit, encompassing 8 male medium secure wards, 5 male low secure wards, 1 adolescent secure ward,1 female low secure ward and 5 female medium secure wards.

Method

Handcuff use was recorded contemporaneously by ward staff in a specialised handcuff proforma. This data were then compiled to assess the number of instances of use, the mental health section applicable to the patient, the reason the patient needed to leave the unit, and the duration of use (including the time period for which the handcuffs were removed during the visit, if applicable.) Data from these forms over an 18 month period were analysed.

Result

Over the 18 months, there were a total of 347 uses of handcuffs, with an average of 18.3 occurrences per month. In 55 cases, the patients were detained under a civil section, with the remaining instances occurring in patients detained under forensic section. 47% were unsentenced prisoners.

The most common destination for patients was the general medical hospital, which accounted for 49% of all visits. Court was the second most common destination, with 39% of uses.

The average duration spent in handcuffs was 3.3 hours. The average time that the handcuffs were taken off during the transfer was 1.2 hours.

Conclusion

Through ongoing education and supervision by the clinical security team, handcuff use in this forensic service was limited to essential situations, most often to allow treatment of physical health issues off-site. A large proportion of instances involved unsentenced prisoners and court attendances, where the risk of absconsion might be particularly high. Duration spent in handcuffs was kept to a minimum, with cuffs being removed where possible. The service strives to continue such good practices and to identify further ways to reduce handcuff use, such as using video-conferencing as an alternative court attendance.
Κοσμολογία στη Θεωρία Einstein - Aether
Authors: Ρουμελιώτης Μιχαήλ
Published: June 2021

Στην διατριβή αυτή παρουσιάζουμε αρχικά τον χώρο λύσεων των εξισώσεων πεδίου της θεωρίας Eistein-Aether για την περίπτωση του χωρόχρονου FLRW καθώς και για την περίπτωση του χωρόχρονου Locally Rotationally Symmetric (LRS) Bianchi Type III . Στην περίπτωση του FLRW βρίσκουμε ανηγμένες Λαγκρανζιανές που αναπαράγουν σωστά τις εξισώσεις κίνησης. Οι εξισώσεις αυτές δεν επιδέχονται λύσεις για όλο τον χώρο των αρχικών παραμέτρων. Οι ανηγμένες Λαγκρανζιανές συνάγονται μέσω ολοκλήρωσης των μη ουσιωδών συντεταγμένων στην ολική δράση και περιγράφουν σωστά την δυναμική οποτεδήποτε υπάρχουν λύσεις των εξισώσεων. Τελικά στην FLRW περίπτωση υπάρχει μια ανωμαλία καμπυλότητας, ενώ στην περίπτωση του Bianchi Type III υπάρχουν επιλογές του εύρους των παραμέτρων για τις οποίες δεν υπάρχει ανωμαλία καμπυλότητας. Στην συνέχεια παρουσιάζουμε τον χώρο λύσεων για τις εξισώσεις πεδίου της θεωρίας Eistein-Aether για την περίπτωση του χωρόχρονου vacuum Bianchi Type V . Βρίσκουμε τμήματα του πεδίου ορισμού των αρχικών παραμέτρων για τα οποία οι ανηγμένες εξισώσεις πεδίου δεν επιδέχονται καμία λύση. Οποτεδήποτε υπάρχουν λύσεις εξετάζεται η φυσική τους ερμηνεία μέσα απο την συμπεριφορά των βαθμωτών Ricci και Kretschmann, καθώς επίσης και η ταυτοποίηση του τελεστή ενέργειας-ορμής σε σχέση με ένα ιδανικό ρευστό. Υπάρχουν περιπτώσεις όπου δεν παρατηρείται καμία ανωμαλία και άλλες όπου το ενεργό ρευστό είναι ισοτροπικό.
Technologies for an inclusive robotics education
Authors: ALIMISIS Dimitris
Published: June 2021

The H2020 project “INBOTS: Inclusive Robotics for a Better Society” (2018­–21) has worked in different disciplines involved in the acceptance and uptake of interactive robotics, including the promotion of accessible and multidisciplinary education programs. In INBOTS, educational robotics is considered as a learning tool that can bring robotics into school classrooms and benefit all children regardless of their future educational or professional orientation. Aiming to make robotics education inclusive, INBOTS has introduced a paradigm shift inspired by sound pedagogies (Papert’s constructionism) and emerging educational trends (the maker movement) and focused on creativity and other 21st-century skills. However, the realisation of this new paradigm requires appropriate curricula and technologies at both hardware and software levels. This paper addresses several questions and dilemmas related to the technologies currently in use in robotics education and the kind of technologies that can best support the proposed paradigm. This discussion results in specific criteria that robotics technologies must fulfil to foster the new paradigm. Based on these criteria, we review some representative technologies in both hardware and software. Then, we identify and discuss some technological solutions that exemplify the kind of technologies that can best support inclusive robotics education and make the proposed paradigm feasible. Finally, we show how some of these technologies can be combined to design a creative and inclusive project consistent with the criteria set in this paper.
Measuring the impact of publicly funded open innovation programmes: the case of Data Market Services Accelerator
Authors: Priestley Maria , Simperl Elena , Juc Cristina , Anguiano María
Published: June 2021

One of the current goals of the European Commission is to stimulate the development and uptake of data and AI technologies in the economy. Substantial funding has been invested in programmes that help startups and small-medium enterprises (SMEs) to assimilate the latest technical and regulatory trends. In order to assess the efficacy and impact of such initiatives, their specific social and economic objectives must be taken into consideration. Our paper proposes a generalisable mixed-methods approach for assessing the impact of publicly funded innovation programmes across multiple dimensions, including their effect on the market, fundraising capabilities of companies, innovation, and socio-economic aspects. We apply this framework to evaluate the recent performance of the Data Market Services (DMS) Accelerator, a current programme funded by the European Commission. In addition to assessing how DMS has been able to meet its objectives, our examination alerts other similar programmes of the challenges in assessing specific outcomes such as standardisation and long-term legal strategy in the fields of data innovation.
Prehospital clopidogrel use and STEMI management: a review
Authors: Hollier Rachelle , Sealy Madison , Ross Nathan , Ebbs Phillip
Published: June 2021

Clopidogrel is an anticoagulant commonly used in the prehospital environment for the management of ST-elevation myocardial infarction (STEMI). Some ambulance services have incorporated this into their treatment regimens; however, others hold a variety of alternative pharmacological interventions. This study examines and determine the pharmacological efficacy and safety of clopidogrel in the management of patients with STEMI and assess whether ambulance services should use the drug as part of standard practice. A literature review was conducted to identify articles relating to the administration of clopidogrel in the prehospital setting. Fourteen peer-reviewed journal articles and eight clinical practice guidelines from international ambulance services were included in this review. According to this review, clopidogrel has been deemed safe, effective and practical for widespread use in the prehospital environment for the management of STEMI. However, some disagreement has arisen over whether clopidogrel is a more favourable anticoagulant than ticagrelor and prasugrel. Anticoagulants such as clopidogrel should be strongly considered as a standard treatment regimen in the prehospital management of STEMI across international jurisdictions.
The Application of the Tissue Microarray (TMA) Technology to Analyze Cerebral Organoids
Authors: Biunno Ida , Paiola Emanuela , De Blasio Pasquale
Published: June 2021

“Multi-Omics” technologies have contributed greatly to the understanding of various diseases by enabling researchers to accurately and rapidly investigate the molecular circuitry that connects cellular systems. The tissue-engineered, three-dimensional (3D), in vitro disease model “organoid” integrates the “omics” results in a model system, elucidating the complex links between genotype and phenotype. These 3D structures have been used to model cancer, infectious disease, toxicity, and neurological disorders. Here, we describe the advantage of using the tissue microarray (TMA) technology to analyze human-induced pluripotent stem cell–derived cerebral organoids. Compared with the conventional processing of individual samples, sectioning and staining of TMA slides are faster and can be automated, decreasing labor and reagent costs. The TMA technology faithfully captures cell morphology variations and detects specific biomarkers. The use of this technology can scale up organoid research results in at least two ways: (1) in the number of specimens that can be analyzed simultaneously and (2) in the number of consecutive sections that can be produced for analysis with different probes and antibodies.
Loss of zebrafish atp6v1e1b, encoding a subunit of vacuolar ATPase, recapitulates human ARCL type 2C syndrome and identifies multiple pathobiological signatures
Authors: Pottie Lore , Van Gool Wouter , Vanhooydonck Michiel , Hanisch Franz-Georg , Goeminne Geert , Rajkovic Andreja , Coucke Paul , Sips Patrick , Callewaert Bert
Published: June 2021

The inability to maintain a strictly regulated endo(lyso)somal acidic pH through the proton-pumping action of the vacuolar-ATPases (v-ATPases) has been associated with various human diseases including heritable connective tissue disorders. Autosomal recessive (AR) cutis laxa (CL) type 2C syndrome is associated with genetic defects in the ATP6V1E1 gene and is characterized by skin wrinkles or loose redundant skin folds with pleiotropic systemic manifestations. The underlying pathological mechanisms leading to the clinical presentations remain largely unknown. Here, we show that loss of atp6v1e1b in zebrafish leads to early mortality, associated with craniofacial dysmorphisms, vascular anomalies, cardiac dysfunction, N-glycosylation defects, hypotonia, and epidermal structural defects. These features are reminiscent of the phenotypic manifestations in ARCL type 2C patients. Our data demonstrates that loss of atp6v1e1b alters endo(lyso)somal protein levels, and interferes with non-canonical v-ATPase pathways in vivo. In order to gain further insights into the processes affected by loss of atp6v1e1b, we performed an untargeted analysis of the transcriptome, metabolome, and lipidome in early atp6v1e1b-deficient larvae. We report multiple affected pathways including but not limited to oxidative phosphorylation, sphingolipid, fatty acid, and energy metabolism together with profound defects on mitochondrial respiration. Taken together, our results identify complex pathobiological effects due to loss of atp6v1e1b in vivo.
Forward genetics in Wolbachia: Regulation of Wolbachia proliferation by the amplification and deletion of an addictive genomic island
Authors: Duarte Elves H. , Carvalho Ana , López-Madrigal Sergio , Costa João , Teixeira Luís
Published: June 2021

Wolbachia is one of the most prevalent bacterial endosymbionts, infecting approximately 40% of terrestrial arthropod species. Wolbachia is often a reproductive parasite but can also provide fitness benefits to its host, as, for example, protection against viral pathogens. This protective effect is currently being applied to fight arboviruses transmission by releasing Wolbachia-transinfected mosquitoes. Titre regulation is a crucial aspect of Wolbachia biology. Higher titres can lead to stronger phenotypes and fidelity of transmission but can have a higher cost to the host. Since Wolbachia is maternally transmitted, its fitness depends on host fitness, and, therefore, its cost to the host may be under selection. Understanding how Wolbachia titres are regulated and other aspects of Wolbachia biology has been hampered by the lack of genetic tools. Here we developed a forward genetic screen to identify new Wolbachia over-proliferative mutant variants. We characterized in detail two new mutants, wMelPop2 and wMelOctoless, and show that the amplification or loss of the Octomom genomic region lead to over-proliferation. These results confirm previous data and expand on the complex role of this genomic region in the control of Wolbachia proliferation. Both new mutants shorten the host lifespan and increase antiviral protection. Moreover, we show that Wolbachia proliferation rate in Drosophila melanogaster depends on the interaction between Octomom copy number, the host developmental stage, and temperature. Our analysis also suggests that the life shortening and antiviral protection phenotypes of Wolbachia are dependent on different, but related, properties of the endosymbiont; the rate of proliferation and the titres near the time of infection, respectively. We also demonstrate the feasibility of a novel and unbiased experimental approach to study Wolbachia biology, which could be further adapted to characterize other genetically intractable bacterial endosymbionts.
Multiple imputation of maritime search and rescue data at multiple missing patterns
Authors: Wang Guobo , Ma Minglu , Jiang Lili , Chen Fengyun , Xu Liansheng
Published: June 2021

Based on the missing situation and actual needs of maritime search and rescue data, multiple imputation methods were used to construct complete data sets under different missing patterns. Probability density curves and overimputation diagnostics were used to explore the effects of multiple imputation. The results showed that the Data Augmentation (DA) algorithm had the characteristics of high operation efficiency and good imputation effect, but the algorithm was not suitable for data imputation when there was a high data missing rate. The EMB algorithm effectively restored the distribution of datasets with different data missing rates, and was less affected by the missing position; the EMB algorithm could obtain a good imputation effect even when there was a high data missing rate. Overimputation diagnostics could not only reflect the data imputation effect, but also show the correlation between different datasets, which was of great importance for deep data mining and imputation effect improvement. The Expectation-Maximization with Bootstrap (EMB) algorithm had a poor estimation effect on extreme data and failed to reflect the dataset’s variability characteristics.
Hypoxia-inducible factor prolyl hydroxylase domain inhibitor may maintain hemoglobin synthesis at lower serum ferritin and transferrin saturation levels than darbepoetin alfa
Authors: Ogawa Chie , Tsuchiya Ken , Tomosugi Naohisa , Maeda Kunimi
Published: June 2021

Background

Hypoxia-inducible factor (HIF) prolyl hydroxylase domain inhibitors, which have recently become clinically available for treating renal anemia, are attracting attention for their novel mechanisms of action.

Methods

Relationships of reticulocyte hemoglobin content (CHr), which reflects recent Hb synthesis, with serum ferritin (s-ft) and transferrin saturation (TSAT) were examined in 30 patients on hemodialysis after switching from darbepoetin alfa (DA) to roxadustat (Rox). Iron deficiency was defined as CHr < 32.0 pg. Cutoff values of s-ft and TSAT were determined using receiver operating characteristic curves for the endpoint CHr ≥ 32.0 pg. Logistic analysis was performed with the reference group having s-ft or TSAT below the corresponding cutoff value (low vs high).

Results

With the endpoint CHr ≥ 32.0 pg on Day 0, cutoff values for s-ft and TSAT were respectively 49.7 ng/mL and 21.6% on Day 0 and 35.5 ng/mL and 16.2% on Day 28. With the endpoint CHr ≥ 32.0 pg on Day 28, cutoff values for s-ft and TSAT on Day 0 were 81.6 ng/mL and 23.9%, respectively. According to multivariable logistic analysis, the odds ratios of CHr ≥ 32.0 pg on Day 0 were significantly higher for high TSAT on Day 0 [34.7 (95% CI 2.42–131.0), p<0.003] and Day 28 [24.8 (95% CI 2.75–224.0), p = 0.004]. There were no significant differences by s-ft. Odd ratios of CHr ≥ 32.0 pg on Day 28 were also significantly higher for high s-ft on Day 0 [16.0 (95% CI 1.57–163.0), p = 0.019] and high TSAT on Day 0 [13.5 (95% CI 1.24–147.0), p<0.033].

Conclusions

Our results suggest Hb synthesis was maintained with lower TSAT and s-ft during Rox therapy compared with DA therapy. To avoid iron deficiency during the 4 weeks after switching DA to Rox, ideal s-ft and TSAT levels before the switch are 81.6 ng/mL and 23.9%, respectively.
The effect of caloric restriction on the increase in senescence-associated T cells and metabolic disorders in aged mice
Authors: Yan Xiaoxiang , Imano Natsumi , Tamaki Kayoko , Sano Motoaki , Shinmura Ken
Published: June 2021

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of Programmed Death-1 (PD-1)+ memory-phenotype T cells that are considered “senescence-associated T cells” in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice. Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype cluster of differentiation (CD) 4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells reduced adipose inflammation and improved insulin resistance in aged mice. Taken together with our previous report, these results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases.
Nutrient limitation of algae and macrophytes in streams: Integrating laboratory bioassays, field experiments, and field data
Authors: Mebane Christopher A. , Ray Andrew M. , Marcarelli Amy M.
Published: June 2021

Successful eutrophication control strategies need to address the limiting nutrient. We conducted a battery of laboratory and in situ nutrient-limitation tests with waters collected from 9 streams in an agricultural region of the upper Snake River basin, Idaho, USA. Laboratory tests used the green alga Raphidocelis subcapitata, the macrophyte Lemna minor (duckweed) with native epiphytes, and in situ nutrient-limitation tests of periphyton were conducted with nutrient-diffusing substrates (NDS). In the duckweed/epiphyte test, P saturation occurred when concentrations reached about 100 μg/L. Chlorophyll a in epiphytic periphyton was stimulated at low P additions and by about 100 μg/L P, epiphytic periphyton chlorophyll a appeared to be P saturated. Both duckweed and epiphyte response patterns with total N were weaker but suggested a growth stimulation threshold for duckweed when total N concentrations exceeded about 300 μg/L and approached saturation at the highest N concentration tested, 1300 μg/L. Nutrient uptake by epiphytes and macrophytes removed up to 70 and 90% of the N and P, respectively. The green algae and the NDS nutrient-limitation test results were mostly congruent; N and P co-limitation was the most frequent result for both test series. Across all tests, when N:P molar ratios >30 (mass ratios >14), algae or macrophyte growth was P limited; N limitation was observed at N:P molar ratios up to 23 (mass ratios up to 10). A comparison of ambient periphyton chlorophyll a concentrations with chlorophyll a accrued on control artificial substrates in N-limited streams, suggests that total N concentrations associated with a periphyton chlorophyll a benchmark for desirable or undesirable conditions for recreation would be about 600 to 1000 μg/L total N, respectively. For P-limited streams, the corresponding benchmark concentrations were about 50 to 90 μg/L total P, respectively. Our approach of integrating controlled experiments and matched biomonitoring field surveys was cost effective and more informative than either approach alone.
High human papillomavirus prevalence among females attending high school in the Eastern Cape Province of South Africa
Authors: Mbulawa Zizipho Z. A. , Somdyala Nontuthuzelo I. , Mabunda Sikhumbuzo A. , Williamson Anna-Lise
Published: June 2021

As part of the human papillomavirus (HPV) vaccination strategy in South Africa, it is essential to have information on HPV prevalence, and HPV types distribution among the unvaccinated population. Information on the prevalence of HPV and the distribution of HPV types in adolescents and young women in South Africa’s Eastern Cape Province is minimal. Therefore, this study investigates the prevalence, distribution of HPV types, and factors associated with HPV infection amongst unvaccinated female learners. A sample composed of 213 sexually active female learners attending high schools in the Eastern Cape Province of South Africa; median age 18 years, who provided self-collected vaginal specimens. Roche Linear Array HPV genotyping assay that detects 37 HPV genotypes was used to detect HPV infection. HPV infection was detected in 76.06% (162/213) of participants. Of these 14.55% (31/213) were positive for HPV types targeted by the Cervarix® HPV vaccine (HPV-16 and/or 18), 20.66% (44/213) by Gardasil®4 (HPV-6, -11, -16 and/or -18) and 37.09% (79/213) by Gardasil®9 (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58). HPV-35, commonly detected in cervical cancer cases among women of African ancestry, was frequently detected (9.40%). Participants who reported to have ever consumed alcohol had a significantly higher risk of HPV infection (OR: 2.91, 95% CI: 1.38–6.11, p = 0.005). High HPV prevalence was observed among participants. The high prevalence of HPV types targeted by the Gardasil®9 vaccine encourages the introduction of the Gardasil®9 vaccine. Data from this study will inform both vaccination campaigns and monitor the impact on HPV types after vaccination.
Effect of family "upward" intergenerational support on the health of rural elderly in China: Evidence from Chinese Longitudinal Healthy Longevity Survey
Authors: Shu Zhan , Xiao Jinguang , Dai Xianhua , Han Yu , Liu Yingli
Published: June 2021

As health challenging rural elderly in an aging population, more attention is being paid on impact of family intergenerational support on the health of the elderly. This paper investigates the effects of children’s intergenerational economic support and non-economic support on physical, mental, and functional health of rural elderly in China in the mean while. This paper applies the 2014 Chinese Longitudinal Healthy Longevity Survey (CLHLS), in particular, applying exploratory factor analysis to ascertain latent variables and Structural Equation Model (SEM), and analyzes the impacts of "Upward" intergenerational support on health of rural elderly. As resulted, after controlling the socioeconomic status of the rural elderly, the family “upward” intergenerational support influences the elderly’s physical health at a percentage of 11.7%, mental health 29.8%, and physiological function 12.6%. Moreover, "Upward" economic support has a positive effect on physiological function (P<0.05). "Upward" non-economic support has negative effects on physiological function and mental health (P<0.05), while it has a positive effect on physical health. In addition, economically independent rural elderly are more likely to benefit from the health of "upward" intergenerational support, especially mental health. In particular, those results are robust. "Upward" intergenerational support plays an important role for the health of rural elderly. For the rural elderly of economic independence, to improve the quality of care and spiritual support, it is important to solve the health problems. In addition, it is necessary to build a comprehensive old-age security and support system for family, community, and society jointly to improve the health of the rural elderly.
Basic human values during the COVID-19 outbreak, perceived threat and their relationships with compliance with movement restrictions and social distancing
Authors: Bonetto Eric , Dezecache Guillaume , Nugier Armelle , Inigo Marion , Mathias Jean-Denis , Huet Sylvie , Pellerin Nicolas , Corman Maya , Bertrand Pierre , Raufaste Eric , Streith Michel , Guimond Serge , de la Sablonnière Roxane , Dambrun Michael
Published: June 2021

This study examines the evolution of Schwartz’s Basic Human Values during the COVID-19 outbreak, and their relationships with perceived threat, compliance with movement restrictions and social distancing. An online questionnaire was administered to a heterogeneous sample of French citizens (N= 1025) during the first French lockdown related to the outbreak. Results revealed a significant evolution of values; the conservation value was higher during the outbreak than usual, and both self-enhancement and openness-to-change values were lower during the COVID-19 outbreak than usual. Conservation and perceived threat during the outbreak were robustly and positively related to both compliance with movement restrictions and social distancing. Conservation during the outbreak emerged as a significant partial mediator of the relationship between perceived threat and outcomes (i.e., compliance with movement restrictions and social distancing). Implications of these results for the malleability of values and the COVID-19 modelling are discussed.
Identifying suitable tester for evaluating Striga resistant lines using DArTseq markers and agronomic traits
Authors: Zebire Degife , Menkir Abebe , Adetimirin Victor , Mengesha Wende , Meseka Silvestro , Gedil Melaku
Published: June 2021

A desirable tester that elicits greater genetic difference in Striga resistance among test crosses in a breeding program has not been reported. Therefore, this study was conducted to characterize 30 Striga resistant yellow endosperm maize inbred lines and three testers with varying resistance levels to Striga using DArTseq SNP markers and agronomic traits to identify a suitable tester for resistance hybrid breeding. Marker-based and agronomic trait-based genetic distances were estimated for yellow endosperm maize inbred lines and testers with varying resistance levels to Striga. The Marker-based cluster analysis separated the Striga resistant lines and testers into two distinct groups. Although the susceptible tester (T3) was the most distantly related to the 30 Striga resistant inbred lines, it exhibited a narrower range in genetic distance estimates and poor agronomic performance under Striga infestation in crosses with the resistant lines. In contrast, the resistant tester (T2) showed a broader range in genetic distance estimates in pairs with the 30 resistant lines. Also, it formed many high yielding hybrids with desirable traits under parasite pressure. Furthermore, the most significant positive association between agronomic trait-based and marker-based distance estimates (r = 0.389, P = 0.01) was observed when T2 has paired with the Striga resistant maize inbred lines. It thus appears that T2 may be used as a suitable tester to determine the breeding value of lines in hybrid maize resistance breeding programs. T2 was the most suitable tester, with a tolerant tester (T1) as an alternative tester to characterize the combining ability of Striga resistant maize inbred lines. This result can also encourage other breeders to investigate testers relative discriminating ability with varying levels of resistance in hybrid breeding for resistance to diseases, pests, and other parasitic plants.
Evaluating the safety of two human experimental intestinal ischemia reperfusion models: A retrospective observational study
Authors: Hundscheid Inca H. R. , Schellekens Dirk H. S. M. , Grootjans Joep , Den Dulk Marcel , Van Dam Ronald M. , Beets Geerard L. , Buurman Wim A. , Lenaerts Kaatje , Derikx Joep P. M. , Dejong Cornelis H. C.
Published: June 2021

Background

We developed a jejunal and colonic experimental human ischemia-reperfusion (IR) model to study pathophysiological intestinal IR mechanisms and potential new intestinal ischemia biomarkers. Our objective was to evaluate the safety of these IR models by comparing patients undergoing surgery with and without in vivo intestinal IR.

Methods

A retrospective study was performed comparing complication rates and severity, based on the Clavien-Dindo classification system, in patients undergoing pancreatoduodenectomy with (n = 10) and without (n = 20 matched controls) jejunal IR or colorectal surgery with (n = 10) and without (n = 20 matched controls) colon IR. Secondary outcome parameters were operative time, blood loss, 90-day mortality and length of hospital stay.

Results

Following pancreatic surgery, 63% of the patients experienced one or more postoperative complications. There was no significant difference in incidence or severity of complications between patients undergoing pancreatic surgery with (70%) or without (60%, P = 0.7) jejunal IR. Following colorectal surgery, 60% of the patients experienced one or more postoperative complication. Complication rate and severity were similar in patients with (50%) and without (65%, P = 0.46) colonic IR. Operative time, amount of blood loss, postoperative C-reactive protein, length of hospital stay or mortality were equal in both intervention and control groups for jejunal and colon IR.

Conclusion

This study showed that human experimental intestinal IR models are safe in patients undergoing pancreatic or colorectal surgery.
Temporal discounting in adolescents and adults with Tourette syndrome
Authors: Schüller Canan Beate , Wagner Ben Jonathan , Schüller Thomas , Baldermann Juan Carlos , Huys Daniel , Kerner auch Koerner Julia , Niessen Eva , Münchau Alexander , Brandt Valerie , Peters Jan , Kuhn Jens
Published: June 2021

Tourette syndrome is a neurodevelopmental disorder associated with hyperactivity in dopaminergic networks. Dopaminergic hyperactivity in the basal ganglia has previously been linked to increased sensitivity to positive reinforcement and increases in choice impulsivity. In this study, we examine whether this extends to changes in temporal discounting, where impulsivity is operationalized as an increased preference for smaller-but-sooner over larger-but-later rewards. We assessed intertemporal choice in two studies including nineteen adolescents (age: mean[sd] = 14.21[±2.37], 13 male subjects) and twenty-five adult patients (age: mean[sd] = 29.88 [±9.03]; 19 male subjects) with Tourette syndrome and healthy age- and education matched controls. Computational modeling using exponential and hyperbolic discounting models via hierarchical Bayesian parameter estimation revealed reduced temporal discounting in adolescent patients, and no evidence for differences in adult patients. Results are discussed with respect to neural models of temporal discounting, dopaminergic alterations in Tourette syndrome and the developmental trajectory of temporal discounting. Specifically, adolescents might show attenuated discounting due to improved inhibitory functions that also affect choice impulsivity and/or the developmental trajectory of executive control functions. Future studies would benefit from a longitudinal approach to further elucidate the developmental trajectory of these effects.
Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir
Authors: Immonen Taina T. , Fennessey Christine M. , Lipkey Leslie , Thorpe Abigail , Del Prete Gregory Q. , Lifson Jeffrey D. , Davenport Miles P. , Keele Brandon F.
Published: June 2021

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.