bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in seasonality and sex ratio of scrub typhus: a case study of South Korea from 2003 to 2019 based on wavelet transform analysis
Authors: Kim Jeehyun , Vounatsou Penelope , Chun Byung Chul
Published: September 2024

Background

Scrub typhus (ST, also known as tsutsugamushi disease) is a common febrile vector-borne disease in South Korea and commonly known as autumn- and female-dominant disease. Although understanding changes in seasonality and sex differences in ST is essential for preparing health interventions, previous studies have not dealt with variations in periodicity and demographic characteristics in detail. Therefore, we aimed to quantify the temporal dynamics of seasonal patterns and sex differences in the incidence of ST in South Korea.

Methods

We extracted epidemiological week (epi-week)-based ST cases from 2003 to 2019 Korean National Health Insurance Service data (ICD-10-CM code: A75.3). To determine changes in seasonality and sex differences, year-, sex-, and age-group-stratified male-to-female ratios and wavelet transform analyses were conducted.

Results

Between 2003 and 2019, 213,976 ST cases were identified. The incidence per 100,000 population increased by 408.8% from 9.1 in 2003 to 37.2 in 2012, and subsequently decreased by 59.7% from 2012 to 15.0 in 2019. According to the continuous wavelet transform results, ST exhibited a dual seasonal pattern with dominant seasonality in autumn and smaller seasonality in spring from 2005 to 2019. Overall, the periodicity of seasonality decreased, whereas its strength decreased in autumn and increased in spring. With an overall male-to-female ratio being 0.68:1, the ratio has increased from 0.67:1 in 2003 to 0.78:1 in 2019 (Kendall’s τ = 0.706, p < 0.001). However, interestingly, the ratio varied significantly across different age groups.

Conclusions

Our findings quantitatively demonstrated changes in seasonality with dual seasonal pattern and shortened overall periodicity and a decrease in sex differences of ST in South Korea. Our study suggests the need for continuous surveillance on populations of vector and host to address ST dynamics to preemptively prepare against global warming.
Exploring clinical markers of Axon degeneration processes in Chemotherapy-induced peripheral neuropathy among young adults receiving vincristine or paclitaxel
Authors: Knoerl Robert , Mazzola Emanuele , Pazyra-Murphy Maria , Ryback Birgitta , Frazier A. Lindsay , Freeman Roy L. , Hammer Marilyn , LaCasce Ann , Ligibel Jennifer , Luskin Marlise R. , Berry Donna L. , Segal Rosalind A.
Published: September 2024

Background

Approximately 70% of patients receiving neurotoxic chemotherapy (e.g., paclitaxel or vincristine) will develop chemotherapy-induced peripheral neuropathy. Despite the known negative effects of CIPN on physical functioning and chemotherapy dosing, little is known about how to prevent CIPN. The development of efficacious CIPN prevention interventions is hindered by the lack of knowledge surrounding CIPN mechanisms. Nicotinamide adenine dinucleotide (NAD+) and cyclic-adenosine diphosphate ribose (cADPR) are potential markers of axon degeneration following neurotoxic chemotherapy, however, such markers have been exclusively measured in preclinical models of chemotherapy-induced peripheral neuropathy (CIPN). The overall objective of this longitudinal, observational study was to determine the association between plasma NAD+, cADPR, and ADPR with CIPN severity in young adults receiving vincristine or paclitaxel.

Methods

Young adults (18–39 years old) beginning vincristine or paclitaxel were recruited from Dana-Farber Cancer Institute. Young adults completed the QLQ-CIPN20 sensory and motor subscales and provided a blood sample prior to starting chemotherapy (T1) and at increasing cumulative vincristine (T2: 3–5 mg, T3: 7–9 mg) and paclitaxel (T2: 300–500 mg/m2, T3: 700–900 mg/m2) dosages. NAD+, cADPR, and ADPR were quantified from plasma using mass spectrometry. Metabolite levels and QLQ-CIPN20 scores over time were compared using mixed-effects linear regression models and/or paired two-sample tests.

Results

Participants (N = 50) were mainly female (88%), white (80%), and receiving paclitaxel (78%). Sensory and motor CIPN severity increased from T1–T3 (p < 0.001). NAD+ (p = 0.28), cADPR (p = 0.62), and ADPR (p = 0.005) values decreased, while cADPR/NAD+ ratio increased from T1–T3 (p = 0.50). There were no statistically significant associations between NAD + and QLQ-CIPN20 scores over time.

Conclusions

To our knowledge, this is the first study to measure plasma NAD+, cADPR, and ADPR among patients receiving neurotoxic chemotherapy. Although, no meaningful changes in NAD+, cADPR, or cADPR/NAD+ were observed among young adults receiving paclitaxel or vincristine. Future research in an adequately powered sample is needed to explore the clinical utility of biomarkers of axon degeneration among patients receiving neurotoxic chemotherapy to guide mechanistic research and novel CIPN treatments.
Sleep and cognitive outcomes in multiple sclerosis; a systematic review
Authors: Golabi Behnam , Razmaray Hadis , Seyedi-Sahebari Sepideh , Bandehagh Heliya , Hakimzadeh Zahra , Khosroshahi Ailin , Moghaddamziabari Seyedehyasmin , Aghaei Negar , Sanaie Sarvin , Talebi Mahnaz , Naseri Amirreza
Published: September 2024

Background

Multiple sclerosis (MS) is a disabling disease of the central nervous system. People living with MS often have co-existing sleep disorders and cognitive dysfunction. The objective of this study was to scrutinize the relationship between cognitive outcomes and sleep conditions in MS.

Methods

This study followed the Joanna Briggs Institute’s (JBI) and PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science databases were searched and original studies delineating the relationship between sleep status and cognitive findings in MS patients‌ were included. The risk of bias was assessed using the JBI critical appraisal tools.

Results

In the final review, out of 1635 screened records, 35 studies with 5321 participants were included. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and polysomnography were the most common assessment tools for evaluation of sleep condition, and cognitive evaluations were conducted using the tests including Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test (BVMT). Assessing the quality of studies showed no significant bias in most of the included articles. A link between sleep condition and cognitive abilities was suggested in the literature, especially with objective measurement of sleep condition; however, current evidence did not support a substantial association between self-reported sleep quality and processing speed and working memory in patients with MS.

Discussion

Evidence proposes sleep is an independent factor associated with cognitive outcomes in MS. Given the limitations of the evidence such as the lack of well-designed prospective studies, these findings need to be interpreted with caution.
Arts, culture and sports engagement and self-rated health: a cross-sectional population-based study in southern Sweden
Authors: Lindström Martin , Pirouzifard Mirnabi , Jensen Anita
Published: September 2024

Background

International research demonstrates an association between arts and culture activities and health and wellbeing. A similar association exists for sports event attendance and health. The aim of this study was to investigate associations between arts and culture engagement and attending sports events during the past year and self-rated health (SRH).

Methods

A cross-sectional study. A public health survey with three reminders was sent to a stratified random sample of the adult 18–84 population in Scania in the southernmost part of Sweden in October-December 2019. The weighted response rate was 44%, and 40,087 total respondents were included in the present study. Analyses were performed in logistic regression models with multiple adjustments for age, education, country of birth, leisure-time physical activity (LTPA), smoking, alcohol consumption, and economic stress.

Results

The prevalence of poor SRH was 32.8% among women and 27.6% among men. The prevalence of theatre/cinema attendance was 63.2% among women and 55.2% among men, arts exhibition/museum attendance was 41.0% among women and 36.0% among men, and for sports attendance it was 33.8% among women and 48.2% among men. All items included in the final models showed statistically significant associations with self-rated health in bivariate logistic regression models. In the multiple model, adjusted for all covariates including both men and women, the odds ratios (ORs) of poor SRH were statistically significant OR 1.21 (95% confidence interval: 1.14–1.29) for not visiting theatre/cinema during the past year, OR 1.11 (1.04–1.17) for not visiting arts exhibition and OR 1.31 (1.24–1.39) for not visiting a sports event.

Conclusions

Significant associations between arts and culture engagement and sports event attendance, and SRH were observed, although effect measures were comparatively low for arts and cultural engagement. The results may be useful for informing public health promotion and prevention strategies.
Understanding the interplay between organisational injustice and the health and wellbeing of female police officers: a meta-ethnography
Authors: Illias Mahnoz , Riach Kathleen , Demou Evangelia
Published: September 2024

Background

Female police officers are reported to encounter more bias, discriminatory practices, and inadequate support than their male counterparts and experience poorer health outcomes. This meta-ethnographic review looks beyond individual responsibilities to consider which aspects of policing impact the health and well-being of female police officers.

Methods

Primary qualitative and mixed method studies published between 2000 and 2024 were included. ProQuest (all databases) and Ovid (Medline and Embase) were searched using terms related to health, wellbeing, females, police, and qualitative research. This was a cross-jurisdictional review, with no limit on country of study. In total, twenty-one papers met the inclusion criteria. A seven-phase inductive and interpretative meta-ethnographic technique was employed to synthesise, analyse, and interpret the data.

Results

The data analysis revealed a distinct outcome that demonstrated a strong relationship and substantial impacts of organisational injustice on the health and well-being of female police officers. Our findings showed that organisational injustice, encompassing procedural, relational, distributive, and gendered injustice, significantly influences the health and well-being of female officers. Impacts on mental health were commonly discussed, followed by aspects influencing social health, workplace wellbeing, and physical health. Moreover, the effects of these four forms of organisational injustice and the associated cultural, systemic, and structural risk factors extend beyond the immediate health and wellbeing impacts on the individual female officer through impeding other aspects of their work life, such as career progression and work-life balance, that can further impact long-term health and well-being.

Conclusion

This review highlights the importance of addressing organisational injustice and the cultural, systemic, and structural risk factors within policing to promote healthier and more inclusive workforces for female officers. Policymakers and practitioners should critically examine policies and practices that may appear gender neutral but disproportionately impact women, affecting the health and well-being of female police officers. By addressing these issues, transformative action can be taken to create safer, more supportive, and healthier working environments for female police officers.
Conceptualization and teaching health advocacy in undergraduate medical education: a document analysis
Authors: de Bok Femke E. , Hermans Jessie , Duvivier Robbert J. , Wolff Djoeke , Reijneveld Sijmen. A.
Published: September 2024

Background

Health advocacy is considered to be a core competence for physicians, but it remains unclear how the health advocacy role, despite being described in overarching competency frameworks, is operationalized in undergraduate medical education (UME). This study aimed to identify how health advocacy is conceptualized and taught in undergraduate medical curricula.

Methods

We performed a qualitative analysis of curriculum documents from all eight medical schools in the Netherlands, all of which offered competency-based UME. Thematic analysis was used to code all the documents and generate themes on health advocacy conceptualization and teaching. To categorize the emerging themes, we used the framework of Van Melle et al. for evaluating the implementation of competency-based medical educational programs.

Results

Health advocacy was mostly conceptualized in mission statements about social responsibility of future physicians, related to prevention and promoting health. We found key concepts of health advocacy to be taught mainly in public health and social medicine courses in the bachelor stage and in community-based clerkships in the master stage. Specific knowledge, skills and attitudes related to health advocacy were taught mostly in distinct longitudinal learning pathways in three curricula.

Conclusion

Health advocacy is conceptualized mostly as related to social responsibility for future physicians. Its teaching is mostly embedded in public health and social medicine courses and community-based settings. A wider implementation is warranted, extending its teaching to the full width of medical teaching, with longitudinal learning pathways providing a promising route for more integrative health advocacy teaching.
Clinical decision making under uncertainty: a bootstrapped counterfactual inference approach
Authors: Wu Hang , Shi Wenqi , Choudhary Anirudh , Wang May D.
Published: September 2024

Background

Learning policies for decision-making, such as recommending treatments in clinical settings, is important for enhancing clinical decision-support systems. However, the challenge lies in accurately evaluating and optimizing these policies for maximum efficacy. This paper addresses this gap by focusing on two key aspects of policy learning: evaluation and optimization.

Method

We develop counterfactual policy learning algorithms for practical clinical applications to suggest viable treatment for patients. We first design a bootstrap method for counterfactual assessment and enhancement of policies, aiming to diminish uncertainty in clinical decisions. Building on this, we introduce an innovative adversarial learning algorithm, inspired by bootstrap principles, to further advance policy optimization.

Results

The efficacy of our algorithms was validated using both semi-synthetic and real-world clinical datasets. Our method outperforms baseline algorithms, reducing the variance in policy evaluation by 30% and the error rate by 25%. In policy optimization, it enhances the reward by 1% to 3%, highlighting the practical value of our approach in clinical decision-making.

Conclusion

This study demonstrates the effectiveness of combining bootstrap and adversarial learning techniques in policy learning for clinical decision support. It not only enhances the accuracy and reliability of policy evaluation and optimization but also paves avenues for leveraging advanced counterfactual machine learning in healthcare.
Learning experiences from an online QI fellowship programme during COVID-19 – a qualitative study
Authors: Powell Richard A. , Sisya Kandazi , Sriram Vimal , Myron Rowan
Published: September 2024

Background

During the COVID-19 pandemic in the United Kingdom, multiple aspects of everyday human existence were disrupted. In contrast, almost all levels of educational learning continued, albeit with modifications, including adaptation to virtual—or online—classroom experiences. This pedagogic transition also occurred in the National Institute of Health and Care Research Applied Research Collaboration Northwest London’s (NIHR ARC NWL) Improvement Leader Fellowship, an annual programme focusing on quality improvement (QI). This qualitative study aimed to understand how these changes impacted the Fellows’ learning experience.

Methods

We explored the experiences of two cohorts of programme Fellows (n = 18, 2020–2021 and n = 15, 2021–2022) with focus groups, analysed under a constructivist qualitative research paradigm.

Results

The two primary and four sub-themes that emerged were: Online QI learning experience (benefits and challenges) and Implementing online QI learning (facilitators and barriers). While benefits had three further sub-themes (i.e., digital flexibility, connection between learners, and respite from impact of COVID-19), challenges had four (i.e., lack of interaction, technological challenges and digital exclusion, human dimension, and digital fatigue). While the facilitators had three sub-themes (i.e., mutual and programmatic support, online resource access, and personal resilience), barriers had one (i.e., preventing implementation and lack of protected time).

Conclusion

Despite challenges to in-person ways of working, online learning generally worked for action-orientated QI learning, but changes are needed to ensure the effectiveness of future use of virtual learning for QI. Understanding the challenges of the translation of learning into action is crucial for implementation learning, gaining insight into how improvement Fellows navigated this translation when learning remotely and implementing directly in their workplace is key to understanding the evolving nature of implementation over the pandemic years and beyond.
Assessment of Lactococcus Cremoris preparations for the pre- and post-milking teat disinfection
Authors: Gazzola A. , Zucali M. , Addis M. F. , Bava L. , Morandi S. , Pisanu S. , Pagnozzi D. , Passera A. , Brasca M. , Piccinini R.
Published: September 2024

Good hygienic milking practices including the disinfection of the cow teat skin before and after milking aimed at preventing the occurrence of new intramammary infections (IMI) in dairy cows. This practice is generally performed using disinfectants, and in the current context of attention to the emergence of resistances, it is of greatest interest to evaluate alternative solutions that can expand treatment options. We assessed the efficacy of a pre-dipping and a post-dipping product based on the bacteriocin-containing culture of Lactococcus cremoris strain FT27, as compared to commercial disinfectants. FT27 was selected for the bactericidal activity in vitro against food pathogens. In the present study, it also revealed a high bactericidal activity against the main mastitis pathogens, most likely related to Nisin A production, according to genomic and proteomic analysis. The lactococcus-based preparations were applied in two commercial dairy farms in Northern Italy. Overall, 298 dairy cows were enrolled, 141 in the treated group (TR), and 157 in the control group (CTR). The cows were sampled at quarter level every two weeks for 3 months. During the trial, all cows showed a good health status. The hygiene level for udder, flanks and legs was generally good (on average < 3 score); the udder hygiene was significantly worse (P < 0.01) in the CTR group. The teat apex hyperkeratosis was overall low (on average < 2 score). We recorded no significant differences between the two experimental groups in the Somatic Cell Count (SCC) values and the bacteriological results. The overall frequency of new IMI was low, ranging 0.6 − 0.5% for S. aureus in the TR or CTR group respectively, to 2.6–4.4% for NASM. Regarding Str. spp., the new IMI accounted for 1.7% or 1.9% in the TR or CTR group, respectively. Notably, the incidence of S. aureus new IMI did not increase during the study, even though neither of the two herds segregated the positive cows. The non-inferiority test showed that the Lactococcus-based pre- and post-dipping products had an efficacy comparable to proven commercial disinfectants in maintaining udder health and preventing new IMI, thus representing a possible alternative to current teat dip products.
Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia
Authors: Adeshara Krishna , Di Marco Elyse , Bordino Marco , Gordin Daniel , Bernardi Luciano , Cooper Mark E , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: September 2024

Background

Hyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.

Methods

The acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study.

Results

Levels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations.

Conclusions

Biomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.
Evidence of a bi-directional relationship between heart failure and diabetes: a strategy for the detection of glucose abnormalities and diabetes prevention in patients with heart failure
Authors: Valensi Paul
Published: September 2024

Prevalence of heart failure (HF) and diabetes are markedly increasing globally. In a population of HF patients, approximately 40% have diabetes which is associated with a more severe HF, poorer cardiovascular outcomes and higher hospitalization rates for HF than HF patients without diabetes. Similar trends were shown in HF patients with prediabetes. In addition, the association between HF and renal function decline was demonstrated in patients with or without diabetes. However, the exact prevalence of dysglycemia in HF patients requires further investigation aiming to clarify the most accurate test to detect dysglycemia in this population. The relationship between HF and diabetes is complex and probably bidirectional. In one way, patients with diabetes have a more than two-fold risk of developing incident HF with reduced or preserved ejection fraction than those without diabetes. In the other way, patients with HF, when compared with those without HF, show an increased risk for the onset of diabetes due to several mechanisms including insulin resistance (IR), which makes HF emerging as a precursor for diabetes development. This article provides epidemiological evidence of undetected dysglycemia (prediabetes or diabetes) in HF patients and reviews the pathophysiological mechanisms which favor the development of IR and the risks associated with these disorders in HF patients. This review also offers a discussion of various strategies for the prevention of diabetes in HF patients, based first on fasting plasma glucose and HbA1c measurement and if normal on an oral glucose tolerance test as diagnostic tools for prediabetes and unknown diabetes that should be performed more extensively in those patients. It discusses the implementation of diabetes prevention measures and well-structured management programs for HF patients who are generally overweight or obese, as well as current pharmacotherapeutic options for prediabetes, including sodium–glucose cotransporter 2 inhibitors which are among the pillars of HF treatment and which recently showed a benefit in the reduction of incident diabetes in HF patients. Thus, there is an urgent need of routine screening for dysglycemia in all HF patients, which should contribute to reduce the incidence of diabetes and to treat earlier diabetes when already present.
Sleep and nighttime behavior disorders in older adults: associations with hypercholesterolemia and hypertriglyceridemia at baseline, and a predictive analysis of incident cases at 12 months follow-up
Authors: Hallab Asma ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2024

Introduction

Sleep disorders, particularly insomnia and obstructive sleep apnea, are associated with dyslipidemia in the general population. The study’s aim was to explore the association between pathological Cholesterol and Triglyceride levels, and sleep and nighttime behavior disorders (SNBD) in older adults, whether they might predict SNBD onset, and to emphasize the role of body mass index (BMI) in this association.

Methods

Alzheimer’s Disease Neuroimaging Initiative (ADNI) population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between hypercholesterolemia, hypertriglyceridemia, and SNBD at baseline and at 12 months. Relevant confounders, particularly BMI, were adjusted for.

Results

Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 years (IQR: 68, 78). At baseline, 357 (16%) had SNBD and 327 (18%) at 12 months; 187 of them were incident cases.

There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, P-value = 0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, P-value = 0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, P-value < 0.001).

Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR = 1.43, 95%CI: 1.13,1.80, P-value = 0.003), even after adjustment for confounding factors (adj. OR = 1.36, 95%CI: 1.06,1.74, P-value = 0.016) and (BMI-adj. OR = 1.29, 95%CI: 1.00,1.66, P-value = 0.048). None of the dyslipidemia forms did predict incident cases at 12 months.

Conclusions

Hypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. The association was independent of BMI. None of the dyslipidemia forms did predict incident SNBD over 12 months. Sleep disorders should motivate a systematic screening of dyslipidemia in older adults and vice versa.
AIBP controls TLR4 inflammarafts and mitochondrial dysfunction in a mouse model of Alzheimer’s disease
Authors: Kim Yi Sak , Choi Soo-Ho , Kim Keun-Young , Navia-Pelaez Juliana M. , Perkins Guy A. , Choi Seunghwan , Kim Jungsu , Nazarenkov Nicolaus , Rissman Robert A. , Ju Won-Kyu , Ellisman Mark H. , Miller Yury I.
Published: September 2024

Microglia-driven neuroinflammation plays an important role in the development of Alzheimer’s disease. Microglia activation is accompanied by the formation and chronic expression of TLR4 inflammarafts, defined as enlarged and cholesterol-rich lipid rafts serving as an assembly platform for TLR4 dimers and complexes of other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds TLR4 and selectively targets cholesterol depletion machinery to TLR4 inflammaraft-expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aβ) induced formation of TLR4 inflammarafts in microglia in vitro and in the brain of APP/PS1 mice. Mitochondria in Apoa1bp−/− APP/PS1 microglia were hyperbranched and cupped, which was accompanied by increased reactive oxygen species and the dilated endoplasmic reticulum. The size and number of Aβ plaques and neuronal cell death were significantly increased, and the animal survival was decreased in Apoa1bp−/−APP/PS1 compared to APP/PS1 female mice. These results suggest that AIBP exerts control of TLR4 inflammarafts and mitochondrial dynamics in microglia and plays a protective role in Alzheimer’s disease associated oxidative stress and neurodegeneration.
Neuroinflammatory responses and blood–brain barrier injury in chronic alcohol exposure: role of purinergic P2 × 7 Receptor signaling
Authors: Togre Namdev S. , Mekala Naveen , Bhoj Priyanka S. , Mogadala Nikhita , Winfield Malika , Trivedi Jayshil , Grove Deborah , Kotnala Sudhir , Rom Slava , Sriram Uma , Persidsky Yuri
Published: September 2024

Alcohol consumption leads to neuroinflammation and blood‒brain barrier (BBB) damage, resulting in neurological impairment. We previously demonstrated that ethanol-induced disruption of barrier function in human brain endothelial cells was associated with mitochondrial injury, increased ATP and extracellular vesicle (EV) release, and purinergic receptor P2 × 7R activation. Therefore, we aimed to evaluate the effect of P2 × 7R blockade on peripheral and neuro-inflammation in ethanol-exposed mice. In a chronic intermittent ethanol (CIE)-exposed mouse model, P2 × 7R was inhibited by two different methods: Brilliant Blue G (BBG) or gene knockout. We assessed blood ethanol concentration (BEC), brain microvessel gene expression by using RT2 PCR array, plasma P2 × 7R and P-gp, serum ATP, EV-ATP, number of EVs, and EV mtDNA copy numbers. An RT2 PCR array of brain microvessels revealed significant upregulation of proinflammatory genes involved in apoptosis, vasodilation, and platelet activation in CIE-exposed wild-type animals, which were decreased 15–50-fold in BBG-treated–CIE-exposed animals. Plasma P-gp levels and serum P2 × 7R shedding were significantly increased in CIE-exposed animals. Pharmacological or genetic suppression of P2 × 7R decreased receptor shedding to levels equivalent to those in control group. The increase in EV number and EV-ATP content in the CIE-exposed mice was significantly reduced by P2 × 7R inhibition. CIE mice showed augmented EV-mtDNA copy numbers which were reduced in EVs after P2 × 7R inhibition or receptor knockout. These observations suggested that P2 × 7R signaling plays a critical role in ethanol-induced brain injury. Increased extracellular ATP, EV-ATP, EV numbers, and EV-mtDNA copy numbers highlight a new mechanism of brain injury during alcohol exposure via P2 × 7R and biomarkers of such damage. In this study, for the first time, we report the in vivo involvement of P2 × 7R signaling in CIE-induced brain injury.
Cerebellar tDCS combined with augmented reality treadmill for freezing of gait in Parkinson’s disease: a randomized controlled trial
Authors: Pisano Fabrizio , Mellace Denise , Fugatti Ambra , Aiello Edoardo Nicolò , Diotti Silvia , Curti Beatrice , Giust Alessandra , Marfoli Angelica , Perin Cecilia , De Sandi Angelica , Alimonti Dario , Priori Alberto , Ferrucci Roberta
Published: September 2024

Background

Parkinson’s disease (PD) is often accompanied by gait disorders and freezing of gait (FoG), disabling symptoms that are resistant to conventional dopamine treatments. Given the cerebellum’s connectivity with the motor cortex and basal ganglia, and its implication in PD, combining transcranial direct current stimulation targeting the cerebellum (ctDCS) with physical exercise might improve gait and balance.

Objective

This study aimed to evaluate the effectiveness of a novel rehabilitation approach that combines noninvasive cerebellar stimulation with motor-cognitive training via an augmented reality treadmill (C-Mill VR+) in individuals with PD and FoG.

Methods

Seventeen individuals with PD exhibiting FoG were enrolled in a randomized controlled trial. The participants were randomly assigned to a group receiving motor-cognitive training on the C-Mill VR+ with either ctDCS or sham ctDCS. Assessments were conducted pre-intervention (T0), post-intervention (T1) after 10 sessions, and at 4-week follow-up (T2), using various clinical scales. Additionally, C-Mill assessments of postural stability and gait were conducted at T0 and T1.

Results

Although no significant time*group interactions were observed for any of the clinical variables measured, some were found in the C-Mill measures. Specifically, right lower limb sway in static conditions, both with eyes open (OAD) and eyes closed (OCD), significantly improved at T1 in the ctDCS group compared with the sham group.

Conclusions

C-Mill outcomes indicate that the combined treatment may enhance motor control. Participants who received ctDCS along with augmented reality motor-cognitive training showed better postural stability.
Intraoperative estimation of natural femoral anteversion from proximal femoral osseous orientation during total hip arthroplasty
Authors: Lee Woo-Suk , Yoon Soon-Phil , Lee Ju Hyung , Park Kwan Kyu , Kang Kyoung Tak , Cho Byung-Woo
Published: September 2024

Background

The purpose of this study was to elucidate the relationship between the orientation of the osseous structure of the proximal femur encountered during total hip arthroplasty (THA) and preoperative femoral anteversion (FA).

Methods

Three-dimensional models were constructed using full-length lower extremity computed tomography images from a total of 80 participants. Femoral neck cutting was performed at heights of 5, 10, and 15 mm relative to the lesser trochanter. Following neck cutting, the angles formed by the anterior outer cortex and posterior outer cortex with the posterior condylar line (PCL) were defined as the anterior cortical angle (ACA) and posterior cortical angle (PCA), respectively. Univariate linear regression analysis was conducted using the remaining measurements with FA as the dependent variable.

Results

The mean age of the participants was 60.98 ± 10.82 years (males, 60.50 ± 11.36 years; females, 61.45 ± 10.37 years) (p = 0.697). All cortical angles and FA were larger in women compared to those in men. When comparing measurements by age groups, no statistically significant differences were observed. Univariate linear regression analysis with FA as the dependent variable showed statistical significance for all cortical angles. The adjusted R2 values were 0.711 (ACA5), 0.677 (ACA10), 0.572 (ACA15), 0.493 (PCA5), 0.574 (PCA10), and 0.446 (PCA15).

Conclusion

Natural FA can be inferred from the anterior cortical angle (ACA) from femoral neck cutting plane observed during the THA procedure without preoperative images.

Trial registration

Retrospectively registered.
Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon
Authors: Li Chengxian , Li Xinyu , Niu Ming , Xiao Dake , Luo Ye , Wang Yinkang , Fang Zhi-E. , Zhan Xiaoyan , Zhao Xu , Fang Mingxia , Wang Jiabo , Xiao Xiaohe , Bai Zhaofang
Published: September 2024

Aristolochic acids are a class of naturally occurring compounds in Aristolochiaceae that have similar structural skeletons and chemical properties. Exposure to aristolochic acids is a risk factor for severe kidney disease and urinary system cancer. However, the carcinogenicity of aristolochic acids to the liver, which is the main site of aristolochic acid metabolism, is unclear. Although the characteristic fingerprint of aristolochic acid-induced mutations has been detected in the liver and aristolochic acids are known to be hepatotoxic, whether aristolochic acids can directly cause liver cancer is yet to be verified. This review summarizes the findings of long-term carcinogenicity studies of aristolochic acids in experimental animals. We propose that spatiotemporal heterogeneity in the carcinogenicity of these phytochemicals could explain why direct evidence of aristolochic acids causing liver cancer has never been found in adult individuals. We also summarized the reported approaches to mitigate aristolochic acid-induced hepatotoxicity to better address the associated global safety issue and provide directions and recommendations for future investigation.
Predictors of cardiac disease in duchenne muscular dystrophy: a systematic review and evidence grading
Authors: Landfeldt Erik , Alemán Alberto , Abner Sophia , Zhang Rongrong , Werner Christian , Tomazos Ioannis , Lochmüller Hanns , Quinlivan Ros M. , Wahbi Karim
Published: September 2024

Background

Duchenne muscular dystrophy (DMD) is a rare disease that causes progressive muscle degeneration resulting in life-threatening cardiac complications. The objective of this systematic literature review was to describe and grade the published evidence of predictors of cardiac disease in DMD.

Methods

The review encompassed searches of Embase, MEDLINE ALL, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of cardiac disease in DMD. The certainty of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.

Results

We included 33 publications encompassing 9,232 patients with DMD. We found moderate- to high-quality evidence that cardiac medication (i.e., ACE inhibitors [enalapril and perindopril], β-blockers [carvedilol], and mineralocorticoid receptor antagonists [eplerenone]) are significantly associated with preserved left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular circumferential strain (LVCS). DMD mutations in exons 51 and 52 were found to be significantly associated with lower risk of cardiomyopathy; deletions treatable by exon 53 skipping and mutations in the Dp116 coding region with improved LVEF and prolonged cardiac dysfunction-free survival; and exons 45–50 and 52 with early left ventricular systolic dysfunction (low/very low-quality evidence). We found high-quality evidence that glucocorticoids (deflazacort) are significantly associated with preserved LVEF and improved fractional shortening (FS), and low-quality evidence that glucocorticoids (deflazacort, prednisone, and/or prednisolone) are associated with improved ejection fraction (EF) and lower risk of cardiomyopathy, ventricular dysfunction, and heart failure-related mortality. Full-time mechanical ventilation was found to be significantly correlated with LVEF (low-quality evidence), muscle strength with FS (low-quality evidence), and genetic modifiers (i.e., LTBP4 rs10880 and ACTN3) with LVEF, lower risk of cardiomyopathy and left ventricular dilation (low-quality evidence).

Conclusion

Several sources of cardiac disease heterogeneity are well-studied in patients with DMD. Yet, the certainty of evidence is generally low, and little is known of the contribution of non-pharmacological interventions, as well as the impact of different criteria for initiation of specific treatments. Our findings help raise awareness of prevailing unmet needs, shape expectations of treatment outcomes, and inform the design of future research.
Cognitive impairment in adolescent and adult-onset psychosis: a comparative study
Authors: Zhang TianHong , Wei YanYan , Tang XiaoChen , Xu LiHua , Cui HuiRu , Hu YeGang , Liu HaiChun , Wang ZiXuan , Chen Tao , Li ChunBo , Wang JiJun
Published: September 2024

Background

Cognitive impairment presents in both adolescent-onset(ado-OP) and adult-onset psychosis(adu-OP). Age and neurodevelopmental factors likely contribute to cognitive differences. This study aimed to characterize cognitive functions in ado-OP compared to adu-OP in a clinical population with drug-naive first-episode psychosis(FEP).

Methods

A total of 788 drug-naive patients with FEP and 774 sex- and age-matched healthy controls(HCs) were included. Participants were divided into four groups by whether they were under or over 21 years of age: adolescent-onset FEP(ado-FEP, n = 380), adult-onset FEP(adu-FEP, n = 408), adolescent HC(ado-HC, n = 334), and adult HC(adu-HC, n = 440). Comprehensive cognitive assessments were performed using the MATRICS Cognitive Consensus Battery(MCCB), covers six cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning, and problem-solving. Data analyses were conducted using correlation analyses and binary logistic regression.

Results

The patterns of cognitive domain differences between ado-FEP and adu-FEP were found to be similar to those between ado-HC and adu-HC, whereas cognitive impairments appeared to be more pronounced in patients with adu-OP than ado-OP. The mazes subtest had the maximum effect size(ES) in the FEP(ES = 0.37) and HC(ES = 0.30) groups when comparing the adolescent and adult groups. Cognitive subtests were mostly significantly correlated with negative symptoms, especially for adolescents with FEP, in which all the subtests were significantly correlated with negative symptoms in the ado-FEP group. Better performance in the domains of spatial cognition and problem-solving abilities was more likely in the ado-FEP group than in the adu-FEP group.

Conclusions

These findings suggest cognitive differences between adolescents and adults but similar patterns of affected domains in HCs and patients with FEP. Therefore, the development of targeted cognitive interventions tailored to the specific needs of different age groups appears warranted.
Statistical analysis plan for the SOLUTIONS randomised controlled trial with internal pilot: Solution Focused Brief Therapy (SFBT) in 10–17 year olds presenting at police custody
Authors: Thompson Paul A. , Moody Gwenllian , Coulman Elinor , Owen-Jones Eleri , Patel Faizan , Gray Kylie M. , Hastings Richard P. , Longman Andrea , Lugg-Widger Fiona , Segrott Jeremy , Badger Julia , Flynn Samantha , Langdon Peter E. , Playle Rebecca
Published: September 2024

Background

Within England, children and young people entering police custody are referred to Liaison and Diversion (L&D) teams. These teams liaise with healthcare and other support services aiming to divert children and young people away from the criminal justice system. Although targeted psychological interventions are not typically offered to children and young people by L&D teams, evidence suggests that Solution Focused Brief Therapy (SFBT) leads to a reduction in internalising and externalising behaviour problems.

Methods

A two-arm individually randomised controlled trial (RCT) with internal pilot and process evaluation will be conducted with approximately 448 children and young people aged 10–17 years presenting at police custody suites who are referred to the L&D team or recruited via online routes if they have previously presented at any police custody suite in England. The primary outcome is the Self-Report Delinquency Measure (SRDM) at 6 months post-randomisation. Analyses will be performed using intention-to-treat.

Results

The statistical analysis plan (SAP) for the trial is described. The plan details of analyses to be undertaken which will be reported in the primary and any secondary publications. The plan was developed and published prior to locking our database and unblinding to treatment allocation.

Discussion

This RCT will evaluate the effectiveness of SFBT in reducing offending behaviours in CYP presenting at police custody suites including testing of moderating factors and sensitivity of the primary analyses.

Trial registration

ClinicalTrials.gov ISRCTN14195235. Registered on June 16, 2023.
Liquid-liquid extraction of selenium (IV) ions from hydrochloric acid solution using Aliquat 336 dissolved in kerosene
Authors: Aly Mohamed I. , Rizk S. E.
Published: September 2024

Solvent extraction of selenium(IV) ions from highly concentrated hydrochloric acid using 0.4 mol/L Aliquat 336 dissolved in kerosene was investigated. As a modifying agent, 1-octanol (10% v/v) was added to the organic phase to avoid the third phase formation. The effect of different parameters affecting the liquid-liquid extraction of selenium(IV) such as the acid concentration, shaking time, metal ion concentration in the aqueous phase, loading capacity, diluents, and temperature, was studied. The results indicate that selenium(IV) is extracted efficiently by 0.4 mol/L Aliquat 336 dissolved in kerosene. It was noticed that the extraction increased with the increase in the acid and Aliquat 336 concentrations, reaching an extraction percentage of about 92% at 8 mol/L HCl and 97.1% at 1 mol/L extractant. The extracted organic species is postulated to be [H2SeO2Cl2.2R4NCl]org by using the slope analysis method, and the value of Kex for selenium(IV) extraction was found to be 26.17 ± 2 M− 2. The structure of the extracted organic species was confirmed by FT-IR. The effect of diluents using various aliphatic and aromatic diluents indicated that kerosene is the most preferred diluent. This is owing to safety ground purpose, economic consideration, the lower cost, availability, and lower toxicity. Thermodynamic parameters indicate the endothermic nature for the solvent extraction of selenium(IV) for the investigated system according to the positive value obtained of the enthalpy change (ΔH). Depending on the obtained results, the method was used to recover selenium(IV) from a simulated solution synthesized in hydrochloric acid medium, which is expected in anode slime leach liquor solution.