Miracle-dz/UniFAR-FTUs huggingface dataset:
An Anglocentric History of Anaesthetics and Analgesics in the Refinement of Animal Experiments

Simple Summary In simultaneously describing the history of animal experimentation and the development of anaesthetics and analgesics from an Anglocentric perspective, this article reveals how the latter have considerably refined animal experiments and brought benefits to both science and the animals involved—particularly in the 19th and 20th centuries. The more recent development of training and educational programmes in laboratory animal anaesthesia and their role in maintaining desirable trends in experimental refinement are also described. Abstract Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK) Parliamentary debates on vivisection in the mid-19th century and viewed as “indisputable refinements in animal experimentation” (Russell and Burch 1959), it seemed that an analysis of their role was overdue. This commentary has, in interweaving the history of animal experimentation in the UK with the evolution of anaesthesia, attempted to: (1) clarify the evidence for Russell and Burch’s view; and (2) evaluate anaesthesia’s ongoing contribution to experimental refinement. The history that emerges reveals that the withholding or misuse of anaesthetics and, or analgesics from laboratory animals in the UK has had a profound effect on scientists and indirectly on the attitudes of the British public in general, becoming a major driver for the establishment of the anti-vivisection movement and subsequently, the Cruelty to Animals Act (1876)—the world’s first legislation for the regulation of animal experimentation. In 1902, the mismanaged anaesthetic of a dog in the Department of Physiology, University College London resulted in numerous events of public disorder initiated by medical students against the police and a political coalition of anti-vivisectionists, trade unionists, socialists, Marxists, liberals and suffragettes. The importance of anaesthesia in animal experiments was sustained over the following 150 years as small mammalian species gradually replaced dogs and cats as the principle subjects for vivisection. In discussing experimental refinement in their 1959 report, “The Principles of Humane Experimental Technique” Russell and Burch described anaesthetics as “… the greatest single advance in humane technique, (which) has at the same time been virtually indispensable for the advance of experimental biology”. Since then, the role of anaesthetics and in particular analgesics has become an unavoidable consideration whenever animal experiments are planned and conducted. This has been accompanied by a proliferation of training and educational programmes in laboratory animal anaesthesia.
Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results.

OBJECTIVES Using moderate or ultra hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of magnetic resonance image-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate specific antigen (PSA) response. METHODS Fifty prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with IMRT (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in five fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response. RESULTS The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade one and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade one gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort. CONCLUSION In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile. ADVANCES IN KNOWLEDGE MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.
Traffic noise exposure, cognitive decline, and amyloid‐beta pathology in an AD mouse model

Concerns are growing that exposure to environmental pollutants, such as traffic noise, might cause cognitive impairments and predispose individuals toward the development of Alzheimer's disease (AD) dementia. In this study in a knock‐in mouse model of AD, we investigated how chronic traffic noise exposure (CTNE) impacts cognitive performance and amyloid‐beta (Aβ) pathology. A group of APPNL‐G‐F/NL‐G‐F mice was exposed to CTNE (70 dBA, 8 hr/day for 1 month) and compared with nonexposed counterparts. Following CTNE, an increase in hypothalamic–pituitary–adrenal (HPA) axis responsivity was observed by corticosterone assay of the blood. One month after CTNE, the CTNE group demonstrated impairments in cognitive and motor functions, and indications of anxiety‐like behavior, relative to the control animals. The noise‐exposed group also showed elevated Aβ aggregation, as inferred by a greater number of plaques and larger average plaque size in various regions of the brain, including regions involved in stress regulation. The results support that noise‐associated dysregulation of the neuroendocrine system as a potential risk factor for developing cognitive impairment and Aβ pathology, which should be further investigated in human studies.
Retrospective Analysis of the Long Term Effect of Subgingival Air Polishing in Supportive Periodontal Therapy.

AIM Glycine powder air polishing (GPAP) procedure has become popular. Aim of the analysis was to compare the clinical outcomes during supportive periodontal therapy (SPT) of subgingival application of GPAP with those using sole conventional mechanical debridement (SC). MATERIAL AND METHODS Over a median SPT period of 5.3 years (re-evaluation through last observation), the GPAP-cohort (n=263) received supra-and subgingival biofilm removal with GPAP. Supragingival calculus was removed using curets and sonic scalers here. Patients in the SC-cohort (n=264) were treated with sonic scalers, curets and rubber cup polishing only. Changes in i.e. pocket probing depth (PPD) and furcation involvement were assessed retrospectively. A bootstrapping equivalence testing method in line with the principle of the two one-sided tests (TOST) procedure was used to compare clinical outcomes. RESULTS The GPAP procedure was statistically equivalent to SC regarding the number of sites with stable PPDs (83.3%; IQR 68.8%, 91.0% vs. 84.0%; IQR 77.8%, 90.0%). However, in the GPAP-cohort, a trend towards deterioration in furcation status (no equivalence) was noted. CONCLUSIONS In periodontal maintenance, the use of GPAP instead of mechanical plaque removal does not improve the clinical outcome. It seems to be contraindicated to treat furcation defects with GPAP only.
Communication in interprofessional rehabilitation teams: a scoping review

Abstract Purpose Effective communication in interprofessional rehabilitation teams is essential for optimal patient care. Despite the established importance, it remains unclear how interprofessional communication (IPC) within teams contributes to rehabilitation service delivery. The aim of this scoping review was to investigate how IPC has been described in rehabilitation literature. Methods Databases (Medline, CINAHL, ERIC, Embase, PsychInfo, and Academic Search Complete) were searched for studies including rehabilitation interprofessional communication. Inclusion and exclusion criteria were identified and applied, data were charted, and thematic analysis conducted. Results Twenty-nine papers were identified, and analysis revealed interrelated themes: communication processes, and inputs and effects. Formal communication processes were most prevalent, portraying variability in professional participation and a lack of patient involvement in dialogue and decision making. Inputs and effects were described at an organisational, team and individual level, highlighting the importance of communication throughout the healthcare hierarchy. Conclusions IPC in rehabilitation is central to effective team function and patient care. To further our understanding, empirical studies examining everyday informal IPC, as well as formal ritualised encounters are needed. Additionally, conceptualisations of IPC would benefit from including the patients’ perspective and by using theoretical framing to attend to places, spaces, and artefacts identified in this review.
Dementia in late-onset epilepsy

Objective To determine the risk of dementia after the development of late-onset epilepsy. Methods We used data from the Atherosclerosis Risk in Communities (ARIC) cohort study, which started in 1987 to 1989 with 15,792 mostly Black and White men and women from 4 US communities. We identified late-onset epilepsy (LOE; seizures starting at age 67 or later) from linked Medicare claims data. We used a Cox proportional hazards regression model to evaluate associations between LOE and dementia through 2017 as ascertained from neuropsychological testing, interviews, and hospital discharge surveillance, and we used multinomial logistic regression to assess the risk of dementia and mild cognitive impairment in the subset with full neuropsychological assessments available. We adjusted for demographics and vascular and Alzheimer disease risk factors. Results Of 9,033 ARIC participants with sufficient Medicare coverage data (4,980 [55.1%] female, 1993 [22.1%] Black), 671 met the definition of LOE. Two hundred seventy-nine (41.6%) participants with and 1,408 (16.8%) without LOE developed dementia (p < 0.001). After a diagnosis of LOE, the adjusted hazard ratio for developing subsequent dementia was 3.05 (95% confidence interval 2.65–3.51). The median time to dementia ascertainment after the onset of LOE was 3.66 years (quartile 1–3, 1.28–8.28 years). Interpretation The risk of incident dementia is substantially elevated in individuals with LOE. Further work is needed to explore causes for the increased risk of dementia in this growing population.
Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review

We examined the evidence for intermittent fasting (IF) as a preventative tool to influence β-amyloid in animal models of Alzheimer’s disease (AD). A Scopus, Ovid, PubMed, and Web of Science (WoS), search yielded 29 results using the keywords “amyloid beta”, “intermittent fasting”, “intermittent caloric restriction”, “alternate day fasting”, “modified alternate-day fasting”, “time-restricted feeding”, “Ramadan fast”, “intermittent calori* restriction”, “intermittent restrictive diet”, and “Alzheimer*”. Five research articles addressed directly the effects of intermittent fasting on β-amyloid levels in animal models of AD: alternate day fasting (ADF) and time-restricted feeding (TRF) methods were incorporated in these studies. The study designs were found to be heterogeneous. Variations in the levels of β-amyloid peptides or plaque in either the hippocampus, cortical areas, or both in animals following dietary intervention were observed as compared to the ad libitum group. Non-significant changes were observed in three studies, while two studies interestingly demonstrated amelioration and reduction in β-amyloid levels. Given the conflicting results obtained from this study, significant care has to be taken into consideration before the protocol can be applied as a preventative approach to treat Alzheimer’s disease. Longitudinal research is warranted to fully grasp how dietary habits can help alleviate the disease either through upstream or downstream of AD pathology.
Screw‐in‐screw fixation of fragility sacrum fractures provides high stability without loosening—biomechanical evaluation of a new concept

Surgical treatment of fragility sacrum fractures with percutaneous sacroiliac (SI) screw fixation is associated with high failure rates. Turn‐out is detected in up to 20% of the patients. The aim of this study was to evaluate a new screw‐in‐screw implant prototype for fragility sacrum fracture fixation. Twenty‐seven artificial hemipelvises were assigned to three groups (n = 9) for instrumentation of an SI screw, the new screw‐in‐screw implant prototype, ora transsacral screw. Before implantation, a vertical osteotomy was set in zone 1 after Denis. All specimens were biomechanically tested to failure in upright position. Validated setup and test protocol were used for complex axial and torsional loading applied through the S1 vertebral body to promote turn‐out of the implants. Interfragmentary movements were captured via optical motion tracking. Screw motions were evaluated by means of triggered anteroposterior X‐rays. Interfragmentary movements and implant motions were significantly higher for SI screw fixation compared to both transsacral and screw‐in‐screw fixations. In addition, transsacral screw and screw‐in‐screw fixations revealed similar construct stability. Moreover, screw‐in‐screw fixation successfully prevented turn‐out of the implant that remained during testing at 0° rotation for all specimens. From biomechanical perspective, fragility sacrum fracture fixation with the new screw‐in‐screw implant prototype provides higher stability than an SI screw, being able to successfully prevent turn‐out. Moreover, it combines the higher stability of transsacral screw fixation with the less risky operational procedure of SI screw fixation and can be considered as their alternative treatment option.
Association between Physical Activity and Mood States of Children and Adolescents in Social Isolation during the COVID-19 Epidemic

The COVID-19 epidemic adversely affects the lifestyle of people. This study aimed to examine the impacts of social isolation on physical activity (PA) levels and mood states of children and adolescents and to explore the correlation between them during the COVID-19 epidemic. A total of 9979 children and adolescents (11.63 ± 1.23 years old) from Yan’an, China volunteered to participate in this study and completed online questionnaires. PA and mood states were measured by International Physical Activity Questionnaire Short Form (IPAQ-SF) and Profile of Mood States (POMS), respectively. The results showed that the mean of students’ moderate-to-vigorous PA (MVPA) was 23.19 min per day. The total mood disturbance in the moderate and high-level PA groups were significantly lower than those in the low-level PA group (p < 0.05). Additionally, boys and girls had significant differences in PA levels (p < 0.01), and the PA levels of students in different grades were also significantly different (p < 0.01). Meanwhile, boys’ mood states were worse than girls’. The Grade 4 in primary schools had the worst mood states while Grade 5 had the best mood states. The results suggested that the MVPA of students has dropped badly, compared with the results of previous studies investigated in normal times. In addition, the PA level had a significantly positive impact on the mood states of children and adolescents during the COVID-19 epidemic. Sex and grades were factors which affected the PA levels and mood states. This study can help policymakers and healthcare professionals understand PA and mood states of Chinese children and adolescents during the epidemic. We should pay attention to the changes in PA levels and mood states of children and adolescents.
Irisin Gene Delivery Ameliorates Burn-Induced Sensory and Motor Neuropathy

Burn-related neuropathy is common and often involves pain, paresthesia, or muscle weakness. Irisin, an exercise-induced myokine after cleavage from its membrane precursor fibronectin type III domain-containing 5 (FNDC5), exhibits neuroprotective and anti-inflammatory activities. A rat model of third-degree burn on the right hind paw was used to investigate the therapeutic role of irisin/FNDC5. Rats received burn injury and were treated with intrathecal recombinant adenovirus containing the irisin sequence (Ad-irisin) at 3 weeks postburn. One week later, mechanical allodynia was examined. The expression of irisin in cerebrospinal fluid (CSF) was detected. Ipsilateral gastrocnemius muscle and lumbar spinal cord were also obtained for further investigation. Furthermore, the anti-apoptotic effect of recombinant irisin in SH-SY5Y cells was evaluated through tumor necrosis factor alpha (TNFα) stimulus to mimic burn injury. We noted intrathecal Ad-irisin attenuated pain sensitization and gastrocnemius muscle atrophy by modulating the level of irisin in CSF, and the expression of neuronal FNDC5/irisin and TNFα in the spinal cord. Ad-irisin also ameliorated neuronal apoptosis in both dorsal and ventral horns. Furthermore, recombinant irisin attenuated TNFα-induced SH-SY5Y cell apoptosis. In summary, irisin attenuated allodynia and muscle wasting by ameliorating neuroinflammation-induced neuronal apoptosis.
Morphology and molecular phylogeny of Hyalosynedra lanceolata sp. nov. and an extended description of Hyalosynedra (Bacillariophyta)

ABSTRACT The araphid diatom genus Hyalosynedra is a very common component of marine benthic communities, occurring as an epiphyte or colonizing hard substrata, and has a worldwide distribution. The hyaline appearance of the valve and the high striation density, which is indiscernible under a light microscope, makes the identification of most species difficult and very few studies have investigated their morphology, phylogeny or ecology in detail. In an extensive study of diatom communities from the hypersaline Mar Menor coastal lagoon (SE Spain), several new taxa were found. Herein we propose Hyalosynedra lanceolata sp. nov. based on morphological observations (light and electron microscopy) and molecular data (phylogenetic and sequence divergence analyses). The species has distinctive morphological characters (radiate colony, biseriate striation, lanceolate sternum and two long laminar lobed chloroplasts) that are new for the genus and have been included in a proposal to extend the genus description. Our results also show that H. toxoneides does not belong to Hyalosynedra, but appears to be more closely related to Thalassionema and Thalassiothrix. However, further molecular and morphological research is needed to clarify its taxonomic position.
Nurses’ Opinions on Do-Not-Resuscitate Orders

The aim of this study was to determine nurses’ opinions on Do Not Resuscitate (DNR) orders. This is a descriptive study. A total of 1250 nurses participated in this study. The mean age of participants was 34.5 ± 7.7 years; 92.6% were women; 56.4% had bachelor’s degrees, and 28.8% were intensive care, oncology, or palliative care nurses. Most participants (94.3%) agreed that healthcare professionals involved in DNR decision-making processes should have ethical competence, while they were mostly undecided (43%) about the statement whether or not DNR should be legal. More than half the participants (60.2%) disagreed with the idea that DNR implementation causes an ethical dilemma. Participants’ opinions on DNR decisions significantly differed according to the number of years of employment and unit of duty. The results showed that most of the nurses had positive attitudes towards DNR orders despite it being illegal. Future studies are needed to better understand family members’ and decision makers’ perceptions of DNR orders for patients.
Estimating the optimal interval between rounds of indoor residual spraying of insecticide using malaria incidence data from cohort studies

Background Indoor residual spraying (IRS) reduces vector densities and malaria transmission, however, the most effective spraying intervals for IRS have not been well established. We estimated the optimal timing interval for IRS using a statistical approach. Methods Six rounds of IRS were implemented in Tororo District, a historically high malaria transmission setting in Uganda, during the study period (3 rounds with bendiocarb active ingredient (Ficam®): December 2014 to December 2015, and 3 rounds with pirimiphos methyl active ingredient (Actellic 300®CS): June 2016 to July 2018). A generalized additive model was used to estimate the optimal timing interval for IRS based on the predicted malaria incidence. The model was fitted to clinical incidence data from a cohort of children aged 0.5–10 years from selected households observed throughout the study period. Results 494 children, 67% aged less than 5 years at enrolment were analysed. Six-months period incidence of malaria decreased from 2.96 per person-years at the baseline to 1.74 following the first round of IRS and then to 0.02 after 6 rounds of IRS. The optimal time interval for IRS differed between bendiocarb and pirimiphos methyl and by IRS round. To retain an optimum impact, bendiocarb would require respraying 17 (95% CI: 14.2–21.0) weeks after application whereas pirimiphos methyl could remain impactful for 40 (95% CI: 37.0–42.8) weeks, although in the final year this estimates 36 (95% CI: 32.7–37.7) weeks. However, we could not estimate from the data the optimal time after the second and third rounds of bendiocarb and after the second round of pirimiphos methyl. Neither the amount of rainfall nor the EIR nor the distribution of nets were found to be statistically significant for determining the time period between spray rounds. Conclusion In our setting, the effect of the two IRS products was distinct. Statistically, pirimiphos methyl provided a longer window of protection than bendiocarb, although impact varied between different spray rounds and years which was not explained by rainfall or EIR or distribution of nets in our statistical approach. Understanding the effectiveness of IRS and how long it lasts can help for planning campaigns, but one should consider the financial cost and insecticide resistance. Monitoring the timing of spray campaigns using clinical incidence could be repeated in future programs to help determine the average period of protectivity of these products.