bluuebunny/crossref_metadata_2025 huggingface dataset:
The abandonment of the ideal of wilderness: Rewilding as the consequence of the Anthropocene metaphysics on restoration ecology
Authors: Arias Sergio
Published: August 2024

The idea of wilderness is being abandoned in restoration ecology due to metaphysical changes in the conception of nature. These changes are associated with the hybridization of nature and culture, an ontological distinction of modernity that touches its end in the Anthropocene. The notion of wilderness is falling because it was based on a static idea of nature, inherited from the modern conception of nature as passive, and this is affecting ecological restoration practices. The pursuit of wilderness has been abandoned in favor of wildness, vindicated by the so-called “rewilding philosophy.” Both restoration ecology and rewilding are based on the same corpus of ecology, but the first has historically operated in a period under the modern ontological distinction between nature and culture, while the second operates already in the hybridization of both categories. Rewilding does not pursue wilderness, no longer possible in the hybrid Anthropocene, but aims to restore the spontaneous order of the wildness.
Book review: Radmila Švarˇícˇková Slabáková (Ed.), Family Memory: Practices, Transmissions and Uses in a Global Perspective
Authors: Bhandari Siddhi
Published: August 2024

Radmila Švarˇícˇková Slabáková (Ed.), Family Memory: Practices, Transmissions and Uses in a Global Perspective (New Delhi: Routledge, 2021), 260 pp. £36.99, ISBN: 9780367701741 (Paperback).
Characterization and Calibration of Cold-Alcohol Plasma Fractionation Intermediates by Kjeldahl Digestion and Digital Refractometry
Authors: Pichler Sandra , Herbinger Karin , Weber Alfred , Anderle Heinz , Gnauer Lucia
Published: August 2024

Background

Almost 80 years after implementation of the industrial ethanol fractionation process, based on the pioneering work of Edwin J. Cohn's research group, it has not lost its importance in providing life-saving biotherapies to patients. The focus has shifted from albumin, which was first used to treat intensive care patients, to immunoglobulin G preparations. Nowadays the latter enables effective, life-long treatment of patients suffering from immunodeficiencies. Ethanol concentration, pH, temperature, protein, and salt concentration are diligently varied during the Cohn fractionation process to finally yield fractions in which the main plasma proteins are enriched at adequate purity. Total protein concentration of the intermediates, probably not as important as ethanol levels and pH, has nevertheless an indisputable influence on the process’ performance

Objectives

Total protein measurement is therefore a valuable in process-control for versatile process performance monitoring. For this purpose, we investigated the application of analytical digital refractometry.

Design

For our pilot study, we used six consecutive batches of nine relevant intermediates covering Takeda's whole industrial-scale Cohn Fractionation process.

Methods

Total protein concentrations of the intermediates were measured with the method of Kjehldal to obtain reference data and digital analytical refractometry, using 10-kDa ultrafiltration to obtain a protein free permeate serving as a sample-specific blank.

Results and Conclusions

Specific refractive index increment dn/dc values, allowing the calculation of the total protein concentrations by refractive index measurement, were obtained for the Cohn Fractionation intermediates investigated. Thus, analytical digital refractometry, a simple, fast, and robust technique, was shown to be fit for this purpose.
The Impact of Hearing Loss on Diabetes Distress Among Adults With Type 2 Diabetes
Authors: Jacobs Molly M. , Ellis Charles
Published: August 2024

Purpose

The purpose of this study was to assess the combined effects of type 2 diabetes (T2D) and hearing loss on the level of distress in individuals with diabetes.

Methods

The 2021 National Health Interview Survey included 2633 adults (ages 18+) with T2D who reported perceived hearing loss, level of diabetes-related distress, household composition, and demographic characteristics. Logistic regressions evaluated these association between hearing loss and diabetes distress controlling for age, income, region of residence, marital status, rurality, educational attainment, insurance coverage, time since diabetes diagnosis, and household composition. Interaction effects examined differential associations between demographic groups.

Results

About 3.5% of adults with T2D in the sample reported hearing loss, and 70% reported diabetes-related distress. Results indicated that diabetes distress was significantly more likely among individuals with hearing loss (OR = 2.08) relative to their hearing counterparts. Additionally, females (OR = 1.50), low-income earners (OR = 1.84), middle-income earners (OR = 1.41), non-Hispanic Blacks (OR = 1.58), and Hispanics (OR = 1.75) with diabetes had higher odds of reporting diabetes distress. Interaction analyses indicated that non-Hispanic Blacks and Hispanics with hearing loss had a 37% and 19%, respectively, higher likelihood of diabetes distress relative to non-Hispanic Whites with hearing loss.

Conclusion

Diabetes distress was more likely among individuals with hearing loss. These findings suggest the communication challenges of individuals with hearing loss may explain the observed differences in distress.
Implementing primary care behavioral health in Swedish primary care – study protocol for a pragmatic stepped wedge cluster trial
Authors: Larsen Hanna Israelsson , Thomas Kristin , Nordgren Lise Bergman , Ruiz Erica Skagius , Koshnaw Kocher , Nilsen Per
Published: August 2024

Background

Mental health problems represent a large and growing public health concern. Primary care handles most of the patients with mental health problems, but there are many barriers to detection and treatment in this setting, causing under-recognition and under-treatment of patients. The service delivery model Primary Care Behavioral Health (PCBH) shows promise to manage mental health problems in primary care, but more research is needed regarding its effects on multiple levels.

Methods

This project investigates the effectiveness and implementation of a large-scale implementation of PCBH in Region Östergötland, Sweden. The aim is to generate new knowledge concerning the impact of a real-world implementation and use of PCBH in routine primary care. A Pragmatic Stepped-Wedge Cluster Trial will be used: 24 PCBH primary care centres in one region will be compared with 48 standard care centres in three other regions. The model will be implemented sequentially at the PCBH centres according to a staggered timetable. Results will be investigated at patient, staff and organization levels and various forms of data will be collected: (1) local and national registry data; (2) questionnaire data; (3) interview data; and (4) document data.

Discussion

This project investigates the effectiveness and implementation of PCBH in routine primary care. The project could result in improved mental health care for the included patients and contribute to the general good for a wider population who have mental health problems. The project’s study design will make it possible to assess many important effects of the PCBH service delivery model at different levels, providing evidence of the effectiveness (or not) of the PCBH model under routine conditions in primary care. The project has the potential to generate clinically meaningful results that can provide a basis for decisions concerning further implementation and use of the model and thus for future development of mental health care provision in primary care.

Trial registration

NCT05633940, date of registration: 2021–04-21.
Follow-up in a point-of-care diabetic retinopathy program in Pittsburgh: a non-concurrent retrospective cohort study
Authors: Bonilla-Escobar Francisco J. , Eibel Maria Regina , Le Laura , Gallagher Denise S. , Waxman Evan L.
Published: August 2024

Background

The Point-of-Care Diabetic Retinopathy Examination Program (POCDREP) was initiated in 2015 at the University of Pittsburgh/UPMC in response to low diabetic retinopathy (DR) examination rates, a condition affecting a quarter of people with diabetes mellitus (PwDM) and leading to blindness. Early detection and treatment are critical with DR prevalence projected to triple by 2050. Approximately, half of PwDM in the U.S. undergo yearly examinations, and there are reported varying follow-up rates with eye care professionals, with limited data on the factors influencing these trends. POCDREP aimed to address screening and follow-up gap, partnering with diverse healthcare entities, including primary care sites, free clinics, and federally qualified health centers.

Methods

A non-concurrent retrospective cohort study spanning 2015–2018 examined data using electronic health records of patients who underwent retinal imaging. Imaging was performed using 31 cameras across various settings, with results interpreted by ophthalmologists. Follow-up recommendations were made for cases with vision-threatening DR (VTDR), incidental findings, or indeterminate results. Factors influencing follow-up were analyzed, including demographic, clinical, and imaging-related variables. We assessed the findings at follow-up of patients with indeterminate results.

Results

Out of 7,733 examinations (6,242 patients), 32.25% were recommended for follow-up. Among these, 5.57% were classified as having VTDR, 14.34% had other ocular findings such as suspected glaucoma and age-related macular degeneration (AMD), and 12.13% were indeterminate. Of those recommended for follow-up, only 30.87% were assessed by eye care within six months. Older age, marriage, and severe DR were associated with higher odds of following up. Almost two thirds (64.35%) of the patients with indeterminate exams were found with a vision-threatening disease at follow-up.

Conclusion

The six-month follow-up rate was found to be suboptimal. Influential factors for follow-up included age, marital status, and the severity of diabetic retinopathy (DR). While the program successfully identified a range of ocular conditions, screening initiatives must extend beyond mere disease detection. Ensuring patient follow-up is crucial to DR preventing programs mission. Recommended strategies to improve follow-up adherence include education, incentives, and personalized interventions. Additional research is necessary to pinpoint modifiable factors that impact adherence and to develop targeted interventions.
Psychosocial interventions for improving the physical health of young people and adults with attention deficit hyperactivity disorder: a scoping review
Authors: Ward John Headley , McBride Audrey , Price Anna , Delgado Tamsin Newlove
Published: August 2024

Background

Young people and adults with ADHD are at risk of a range of physical health problems. There is limited guidance on how to approach health problems in ADHD, and especially around 16-25 year olds who will be transitioning from paediatric to adult care. The aim of this scoping review was to identify psychosocial interventions that target physical health in young people and adults with ADHD.

Methods

We constructed searches in MEDLINE, PsycInfo, EMBASE of adolescents, young people and adults. Inclusion criteria were; studies of psychosocial interventions examining a component of physical health, applicable to people aged 16-25, with clinical or research diagnoses of ADHD. Data were extracted using a data extraction tool and tabulated, including study intervention framing/aims, population, intervention, and relevant outcomes (including specific statistics where relevant).

Results

Our search identified 22 unique papers covering, psychosocial interventions targeting at least one of sleep (n=7), smoking (n=3), substance/alcohol use (n=4), physical health/exercise (n=6) and general health (n=3). Studies examined psychotherapy/behaviour interventions (n=12), psychoeducation (n=4), digital (n=2) and social interventions (n=4). There was significant heterogeneity in intervention framing, outcome measures and population.

Conclusion

Further work on the impact of targeted physical health interventions, with explicit reference to a conceptual framework of poor health in ADHD is required. Furthermore, future work standardising reporting of physical health outcomes in ADHD is crucial for the development of an evidence base in this field.
Dietary diversity and its association with changes in anthropometric indices of community-dwelling older adults in Tehran, Iran: a longitudinal study (2017–2021)
Authors: Rezaei Mahshid , Forouzan Kimia , Eini-Zinab Hassan , Omidvar Nasrin , Jafaripour Samaneh , Rezazadeh Arezoo
Published: August 2024

Background

Dietary diversity refers to the consumption of a variety of foods or food groups over a given reference period, which is crucial for improving nutrition and overall health. This longitudinal study aimed to investigate the association between dietary diversity and anthropometric indices in community-dwelling older adults living in Tehran in 2017 and 2021.

Methods

The current study was conducted on 368 older adults [204 (55.4%) women and 164 (44.6%) men] over 60 years of age living in Tehran, who were selected by a systematic cluster sampling method at two-time points, 2017 and 2021. Anthropometric measures (weight, height, hip circumference, and waist circumference) were assessed with standard methods. The participants’ dietary intake was assessed by completing two non-consecutive 24-hour recalls, and dietary diversity score (DDS) was calculated based on Kant’s method. Statistical analysis was performed using R software by the mixed effect model method.

Results

The mean DDS of the participants in 2017 (5.07 ± 1.20) was higher than that in 2021 (4.94 ± 1.09) (p < 0.05). DDS and dairy diversity score decreased significantly over time. After adjusting for confounders, there was an inverse relationship between the DDS and Body Mass Index (BMI) (B = -0.22; ﻿SE = 0.09), but the interaction effect of year × DDS (B = 0.19; SE = 0.10﻿) was not significant (p = 0.06). However, there was a positive relationship between the DDS and A Body Shape Index (ABSI) (B = 0.00;﻿ p = 0.022), after adjusting for confounders, this relationship was no longer significant. Additionally, the interaction effect of year and DDS on the ABSI was not significant.

Conclusion

The dietary intake and dietary diversity of older adult residents of Tehran declined dramatically with age, and a higher DDS was associated with improved anthropometric indices. DDS had an inverse relationship with general obesity in the studied participants, and the passage of time did not affect this relationship. The DDS can be used as a predictive index and is a powerful tool for investigating changes in nutritional status in longitudinal studies of old age. However, longer-duration studies are needed to obtain more conclusive results.
Advice to future family physicians: findings from qualitative interviews with family medicine residents and early-career family physicians
Authors: Wang Sean , Buote Richard , Moritz Lauren R. , Lavergne M. Ruth , Marshall Emily Gard
Published: August 2024

Background

Canadians continue to report challenges accessing primary care. Practice choices made by primary care providers shape services available to Canadians. Although there is literature observing family medicine practice trends, there is less clarity on the reasoning underlying primary care providers’ practice intentions. Advice offered by residents and early-career family physicians may reveal challenges they have experienced, how they have adapted to them, and strategies for new residents. In this paper, we examine advice family medicine residents and early-career family physicians would give to new family medicine residents.

Methods

Sixty early-career family physicians and thirty residents were interviewed as part of a mixed-methods study of practice patterns of family medicine providers in Canada. During qualitative interviews, participants were asked, “what advice would you give [a new family medicine resident] about planning their career as a family physician?” We inductively analyzed responses to this question.

Results

Advice consisted of understanding the current climate of family medicine (need for specialization, business management burden, physician burnout) and revealed reasons behind said challenges (lack of support for comprehensive clinic care, practical limitations of different practice models, and how payment models influence work-life balance). Subtheme analyses showed early-career family physicians being more vocal on understanding practical aspects of the field including practice logistics and achieving job security.

Conclusion

Most advice mirrored current changes and challenges as well as revealing strategies on how primary care providers are handling the realities of practicing family medicine. Multi-modal systemic interventions may be needed to support family physicians throughout the changing reality of family medicine and ensure family medicine is an appealing specialty.
An evaluation of a multi-partner approach to increase routine immunization coverage in six northern Nigerian States
Authors: Dougherty Leanne , Adediran Mayokun , Akinola Akinwumi , Alabi Matthew , Etim Eno-Obong , Ohioghame Jane , Adedimeji Adebola
Published: August 2024

Background

Global health partnerships are increasingly being used to improve coordination, strengthen health systems, and incentivize government commitment for public health programs. From 2012 to 2022, the Bill & Melinda Gates Foundation (BMGF) and Aliko Dangote Foundation (ADF) forged Memorandum of Understanding (MoU) partnership agreements with six northern state governments to strengthen routine immunization (RI) systems and sustainably increase immunization coverage. This mixed methods evaluation describes the RI MoUs contribution to improving program performance, strengthening capacity and government financial commitment as well as towards increasing immunization coverage.

Methods

Drawing from stakeholder interviews and a desk review, we describe the MoU inputs and processes and adherence to design. We assess the extent to which the program achieved its objectives as well as the benefits and challenges by drawing from a health facility assessment, client exit interview and qualitative interviews with service providers, community leaders and program participants. Finally, we assess the overall impact of the MoU by evaluating trends in immunization coverage rates.

Results

We found the RI MoUs across the six states to be mostly successful in strengthening health systems, improving accountability and coordination, and increasing the utilization of services and financing for RI. Across all six states, pentavalent 3 vaccine coverage increased from 2011 to 2021 and in some states, the gains were substantial. For example, in Yobe, vaccination coverage increased from 10% in 2011 to nearly 60% in 2021. However, in Sokoto, the change was minimal increasing from only 4% in 2011 to nearly 8% in 2021. However, evaluation findings indicate that issues pertaining to human resources for health, insecurity that inhibits supportive supervision and vaccine logistics as well as harmful socio-cultural norms remain a persistent challenge in the states. There is also a need for a rigorous monitoring and evaluation plan with well-defined measures collected prior to and throughout implementation.

Conclusion

Introducing a multi-partner approach grounded in a MoU agreement provides a promising approach to addressing health system challenges that confront RI programs.
The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain
Authors: Ohm Melanie , Hosseini Shirin , Lonnemann Niklas , He Wei , More Tushar , Goldmann Oliver , Medina Eva , Hiller Karsten , Korte Martin
Published: August 2024

Despite advances in antimicrobial and anti-inflammatory treatment, inflammation and its consequences remain a major challenge in the field of medicine. Inflammatory reactions can lead to life-threatening conditions such as septic shock, while chronic inflammation has the potential to worsen the condition of body tissues and ultimately lead to significant impairment of their functionality. Although the central nervous system has long been considered immune privileged to peripheral immune responses, recent research has shown that strong immune responses in the periphery also affect the brain, leading to reactive microglia, which belong to the innate immune system and reside in the brain, and neuroinflammation. The inflammatory response is primarily a protective mechanism to defend against pathogens and tissue damage. However, excessive and chronic inflammation can have negative effects on neuronal structure and function. Neuroinflammation underlies the pathogenesis of many neurological and neurodegenerative diseases and can accelerate their progression. Consequently, targeting inflammatory signaling pathways offers potential therapeutic strategies for various neuropathological conditions, particularly Parkinson’s and Alzheimer’s disease, by curbing inflammation. Here the blood–brain barrier is a major hurdle for potential therapeutic strategies, therefore it would be highly advantageous to foster and utilize brain innate anti-inflammatory mechanisms. The tricarboxylic acid cycle-derived metabolite itaconate is highly upregulated in activated macrophages and has been shown to act as an immunomodulator with anti-inflammatory and antimicrobial functions. Mesaconate, an isomer of itaconate, similarly reduces the inflammatory response in macrophages. Nevertheless, most studies have focused on its esterified forms and its peripheral effects, while its influence on the CNS remained largely unexplored. Therefore, this study investigated the immunomodulatory and therapeutic potential of endogenously synthesized itaconate and its isomer mesaconate in lipopolysaccharide (LPS)-induced neuroinflammatory processes. Our results show that both itaconate and mesaconate reduce LPS-induced neuroinflammation, as evidenced by lower levels of inflammatory mediators, reduced microglial reactivity and a rescue of synaptic plasticity, the cellular correlate of learning and memory processes in the brain. Overall, this study emphasizes that both itaconate and mesaconate have therapeutic potential for neuroinflammatory processes in the brain and are of remarkable importance due to their endogenous origin and production, which usually leads to high tolerance.
Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance
Authors: Sun Yitian , Li Qinyi , Huang Yufei , Yang Zijing , Li Guohua , Sun Xiaoyu , Gu Xiaoqing , Qiao Yunhao , Wu Qibiao , Xie Tian , Sui Xinbing
Published: August 2024

Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future.

Graphical Abstract
Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation
Authors: Yuan Shyng-Shiou F. , Chan Leong-Perng , Nguyen Hieu D. H. , Su Chang-Wei , Chen Yuk-Kwan , Chen Jeff Yi-Fu , Shimodaira Shigetaka , Hu Stephen Chu‐Sung , Lo Steven , Wang Yen-Yun
Published: August 2024

Background

Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive.

Methods

Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE.

Results

We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters.

Conclusion

Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.
A scalable, chromatography-free, biocatalytic method to produce the xyloglucan heptasaccharide XXXG
Authors: Rodd Andrew M. , Mawhinney William M. , Brumer Harry
Published: August 2024

Xyloglucan oligosaccharides (XyGOs) are highly branched, complex carbohydrates with a variety of chemical and biotechnological applications. Due to the regular repeating pattern of sidechain substitution of the xyloglucan backbone, well-defined XyGOs are readily accessed for analytical and preparative purposes by specific hydrolysis of the polysaccharide with endo-glucanases. To broaden the application potential of XyGOs, we present here an optimized, scalable method to access large quantities of galactosylated XyGOs by treatment of the bulk agricultural by-product, tamarind kernel powder (TKP), with a highly specific endo-xyloglucanase at high-solids content. Subsequent β-galactosidase treatment reduced XyGO complexity to produce exclusively the branched heptasaccharide XXXG (Xyl3Glc4: [α-D-Xylp-(1 → 6)]-β-D-Glcp-(1 → 4)-[α-D-Xylp-(1 → 6)]-β-D-Glcp-(1 → 4)-[α-D-Xylp-(1 → 6)]-β-D-Glcp-(1 → 4)-D-Glcp). The challenge of removing the co-product galactose was overcome by fermentation with baker’s yeast, thereby avoiding chromatography and other fractionation steps to yield highly pure XXXG. This simplified approach employs many of the core concepts of green chemistry and engineering, enables facile production of 100 g quantities of XyGOs and XXXG for laboratory use, and serves as a guide to further production scale-up for applications, including as prebiotics, plant growth effectors and elicitors, and building blocks for glycoconjugate synthesis.
Anti-neuroinflammatory effects of the KIOM -patented Polygonum multiflorum maximized root tuber against LPS-stimulated BV2 Cells
Authors: Oh Tae Woo , Ban Yeongjun , Kang Youngmin
Published: August 2024

The main pathological mechanism of neurodegeneration is neuroinflammation. It is known that the persistent neuroinflammatory response is harmful by causing secondary nerve tissue damage. Meanwhile, P. multiflorum is a traditional oriental medicinal herb. It has been used as a hematopoietic agent and is used to treat a variety of diseases and conditions. The aim of the present study was to compare the anti-inflammatory efficacy between the commonly available P. multiflorum (C1) and the KIOM-patented in vitro-propagated P. multiflorum (K1), which had higher content of active ingredients and biomass, using culture and cultivation conditions of LPS-induced neuroinflammation. After stimulation with LPS and treatment with C1 and K1 in mouse microglial BV-2 cells, nitric oxide (NO) production, pro-inflammatory cytokine secretion, inducible NO synthase (iNOS) expression, MAPK phosphorylation and transcription factor activity were assessed. We examined the antioxidant effect using DPPH and production of nitric oxide (NO). C1 and K1 suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. Furthermore, we determined the levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms. Additionally, C1 and K1 also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. In all experimental results, excellent anti-neuroinflammatory effects were confirmed at a lower dose in K1 than in C1, which is believed to be due to the increased biomass. Therefore, K1 is expected to be more effective than C1 and can be applied more broadly in the development of prevention and treatment of various inflammatory-mediated neurodegenerative diseases.
A risk prediction model for unexplained early neurological deterioration following intravenous thrombolysis
Authors: Zhu Bifeng , Wang Dan , Zuo Jing , Huang Yi , Gao Chang , Jiang Haiwei , Yan Dan
Published: August 2024

Background and objectives

Early neurological deterioration (END) post-intravenous thrombolysis significantly impacts the long-term prognosis of stroke patients. This study aimed to establish a rapid risk prediction model for unexplained END following intravenous thrombolysis.

Methods

This prospective study consecutively enrolled patients with acute ischemic stroke treated with recombinant tissue plasminogen activator intravenous thrombolysis at the Department of Neurology, Third People’s Hospital of Hubei Province, and Yangluo Hospital District between June 2019 and December 2022. Unexplained END was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score between admission and 24 h. A nomogram was developed and assessed by calculating the area under the receiver operating characteristic curve (AUC-ROC). The calibration was assessed using the Hosmer–Lemeshow test.

Results

A total of 211 patients (130 males and 110 patients aged < 65 years) were included, with 66 experiencing unexplained END. Multivariate logistic regression analysis identified large arterial disease, transient ischemic attack, high blood glucose, high neutrophil/lymphocyte ratio, important perforator disease, and low the Alberta Stroke Program Early CT scores (APSECTS) as independent risk factors for END and established the nomogram used above indicators. The nomogram showed an AUC-ROC of 0.809 (95% CI 0.7429–0.8751), with a specificity of 0.862 and sensitivity of 0.712. The positive predictive value was 0.702, and the negative predictive value was 0.868. The Hosmer–Lemeshow goodness-of-fit test (χ2 = 1.069, P = 0.169) indicated acceptable model calibration.

Conclusion

This study successfully established a risk prediction model for END following intravenous thrombolysis and the model demonstrates good stability and predictive capacity. Further validation through a prospective, multicenter study is necessary.
Computational analysis of non-synonymous SNPs in the human LCN2 gene
Authors: Sivakumar Kaniha , Subbiah Usha
Published: August 2024

Background

Lipocalin-2 (LCN2), a neutrophil gelatinase-associated protein, plays an important role in iron homeostasis, infection, and inflammation. Polymorphism in the LCN2 gene is linked to various diseases such as cardiovascular disease, renal damage, and colorectal and pancreatic cancer. Identifying deleterious functional non-synonymous SNPs in the LCN2 gene is crucial in understanding how these genetic variations affect its structure and function.

Methods

Several in silico tools such as SIFT, Polyphen-2, PROVEAN, PREDICT SNP, MAPP, and SNAP2 followed by I-MUTANT 2.0, MUpro, ConSurf, and NetsurfP-2.0, secondary structure of the protein by SOPMA and PSIPRED, while its interaction with other genes and proteins was analyzed using GeneMANIA and STRING, respectively, and AlphaFold for protein's 3D structure prediction.

Results

The study identified 6 potentially harmful nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) and their structure and function were analyzed using prediction tools. I-MUTANT 2.0 predicted an increase in stability with the nsSNPs rs139418967, while the other shows decrease in protein stability with the 6 nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) which was validated using MUpro. ConSurf identified the 6 high-risk nsSNPs to be in the conserved regions of the protein. The result showed that rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, and rs368926734 were found to be highly conserved and the variant amino acids. According to NetsurfP-2.0 server, the result showed that rs11556770 (Q39H), rs139418967 (L6P), rs368926734 (Y135H) were predicted to be exposed and rs142623708 (M71I), rs200107414 (Y52C), rs368926734 (Y135) were buried. The PSIPRED server analysis indicated that the predominant secondary structure was a strand, with lesser occurrences of coil and helix.

Conclusion

Overall, the study identified detrimental nsSNPs of LCN2 using computational analysis which could be used for large population-based investigations and diagnosis.
Expert psychiatric reports for the Parole Board for England and Wales
Authors: Middleton Laura , Daly Lynne , Nathan Rajan
Published: August 2024

The Parole Board for England and Wales advises on the release, recall and licence conditions of a small subgroup of prisoners serving determinate sentences and the majority of those serving indeterminate sentences. Since the establishment of the Parole Board in 1968, the parole process has been shaped and clarified by further legislation and case law. In certain scenarios, psychiatric expert evidence may be sought to inform the Board's determination of whether a prisoner can be safely released into the community. Psychiatrists preparing expert reports for the Parole Board should be familiar with the current operationalisation of parole. This involves an understanding not only of the functioning of the Parole Board, but also of the criminal justice context in which prisoners subject to parole are managed. Having set the scene, by describing the role of the Parole Board and the wider context, this article examines how to undertake assessments and complete psychiatric reports for the Board.
Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022
Authors: Tseretopoulou Xanthippi , Ali Salma R , Bryce Jillian , Amin Nadia , Atapattu Navoda , Bachega Tania A S S , Baronio Federico , Ortolano Rita , Birkebaek Niels H , Bonfig Walter , Cools Martine , Davies Justin H , Thomas Tessy , de Vries Liat , Elsedfy Heba , Amr Nermine H , Flueck Christa E , Globa Evgenia , Guran Tulay , Yavas-Abali Zehra , Guven Ayla , Hannema Sabine E , Iotova Violeta , Konrad Daniel , Lenherr-Taube Nina , Krone Nils P , Leka-Emiri Sofia , Vlachopapadopoulou Elpis , Lichiardopol Corina , Marginean Otilia , Markosyan Renata , Neumann Uta , Niedziela Marek , Banaszak-Ziemska Magdalena , Phan-Hug Franziska , Poyrazoglu Sukran , Probst-Scheidegger Ursina , Randell Tabitha , Russo Gianni , Salerno Mariacarolina , Seneviratne Sumudu , Shnorhavorian Margarett , Thankamony Ajay , Tadokoro-Curraro Rieko , van den Akker Erica , van Eck Judith , Vieites Ana , Wasniewska Malgorzata , Ahmed S Faisal
Published: August 2024

Background

It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events.

Aim

Study temporal trends of AI related AE in the I-CAH Registry.

Methods

In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019.

Results

In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02).

Conclusion

The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.
Frameless Stereotactic Biopsy of Brainstem Tumors Using the Stealth Autoguide: A Technical Note
Authors: Patel Ajay , Hux Nicholas , Virtanen Piiamaria S. , Budnick Hailey , Kazi Fezaan , Tailor Jignesh K.
Published: August 2024

BACKGROUND AND OBJECTIVES:

In the molecular era of neuro-oncology, it is increasingly necessary to obtain tissue for next-generation sequencing and methylome profile for prognosis and targeted oncological management. Brainstem tumors can be technically challenging to biopsy in the pediatric population. Frame-based and frameless techniques have previously been described and proven to be safe and efficacious in children. Recent cranial robotic guidance platforms have augmented the fluency of frameless stereotactic approaches, but the technical nuances of these procedures in children are not often discussed. We present a technical workflow for frameless stereotactic biopsy of brainstem tumors in children using the Medtronic Stealth Autoguide cranial robotic guidance platform and examine safety and efficacy of this surgical approach.

METHODS:

A minimally invasive, frameless, transcerebellar approach is described, including operative steps and workflow. We assessed operative times, diagnostic accuracy and yield, and complication rates.

RESULTS:

Five patients underwent biopsy with the technique described. The youngest patient in our series was of 2 years. The intended target was achieved on postoperative imaging in all cases, and diagnostic tissue was obtained in all 5 patients. One patient had a clinically insignificant hemorrhage.

CONCLUSION:

Frameless stereotactic biopsy of the brainstem can be performed safely, efficiently, and accurately using the Medtronic Stealth Autoguide robotic platform in children as young as 2 years.
Absence of Foramen Spinosum on Computed Tomography Scan Determines Feasibility of Middle Meningeal Artery Embolization
Authors: Hubbard Zachary S. , Cunningham Conor M. , Porto Guilherme , Sowlat Mohammad-Mahdi , Elawady Sameh Samir , Al Kasab Sami , Kicielinski Kimberly , Lena Jonathan , Spiotta Alejandro M.
Published: August 2024

BACKGROUND AND OBJECTIVES:

Middle meningeal artery embolization (MMAE) has emerged as a novel treatment of chronic subdural hematoma. In 0.5% of patients, however, there exists an ophthalmic origin of the middle meningeal artery (MMA) known as the recurrent meningeal artery. It is known that the recurrent MMA is associated with failure of its skeletal aperture, the foramen spinosum, to form during development. The aim of this study was to investigate MMAE feasibility as a function of the presence/absence of the foramen spinosum on preprocedure computed tomography (CT) scan.

METHODS:

We performed a retrospective review of 100 consecutive patients undergoing MMAE from January 2022 to December 2023 at the Medical University of South Carolina. Preprocedure CT scan of the head was reviewed, and the presence or absence of the foramen spinosum, along with laterality, was recorded. Subsequently, angiographic studies were reviewed.

RESULTS:

All patients (n = 100) had preprocedural CT scan available for review. The incidence of an absent foramen spinosum was 3% (n = 3). All absent foramen spinosum were left sided (2F, 1M). All embolization attempts in these patients were aborted due to recurrent meningeal artery. 97% of patients had patent bilateral foramen spinosum (n = 97). Two of these patients possessed partial ophthalmic contribution to the MMA (2%), and embolization was not performed. In patients with patent foramen spinosum, successful embolization was achieved in 92/97 patients (94.8%).

CONCLUSION:

The review of preprocedure CT scan may serve as an opportunity to identify patients with ophthalmic arterial origin of the MMA, subverting unnecessary risks associated with catheter angiography.
Inflammatory and Oxidant Responses to Arduous Military Training: Associations with Stress, Sleep, and Performance
Authors: KARGL CHRISTOPHER K. , GAGE CATHERINE R. , FORSE JENNIFER N. , KOLTUN KRISTEN J. , BIRD MATTHEW B. , LOVALEKAR MITA , MARTIN BRIAN J. , NINDL BRADLEY C.
Published: August 2024

Background

Arduous military training frequently consists of prolonged physical activity, sleep disturbance, and stress that increases musculoskeletal injury risk and performance decrements. Inflammatory and oxidative stress responses have been reported in response to arduous training, but with inconsistencies across markers and with underrepresentation of women. The purpose of the current report was to measure circulating inflammation and oxidative stress responses to military training and to correlate biomarkers with subjective measures of stress and sleep quality as well as military fitness test performance.

Methods

Candidates undergoing the 10-wk Marine Corps Officer Candidate School (OCS; 101 men, 62 women) were monitored, with demographic and questionnaire data collected, and blood drawn before and after OCS. Blood was analyzed for six markers of inflammation and three markers of oxidative stress. Associations between biomarkers and questionnaire and fitness test performance were tested.

Results

All measured inflammatory markers as well as plasma antioxidant capacity were elevated following OCS. The inflammatory increase was higher in women for several markers. Sleep disturbance and stress perception were associated with interleukin (IL)-6, IL-10, and C-reactive protein concentrations, suggesting that low sleep disturbance and stress perception were associated with low inflammatory load. In addition, those with the highest inflammation at each time point performed worse on fitness tests than those with low inflammation.

Conclusions

Following arduous military training, the circulating environment in a significant portion of officer candidates resembled chronic low-grade inflammation. This circulating inflammatory environment appeared worse with poor sleep, high stress perception, and poor fitness test performance, with utility observed for C-reactive protein, IL-6, and IL-10 as biomarkers of these responses. Because inflammation may contribute to musculoskeletal injury and performance decrements, minimizing chronic inflammation during military training should be explored.
Effects of scapulothoracic exercises on chest mobility, respiratory muscle strength, and pulmonary function in male COPD patients with forward shoulder posture: A randomized controlled trial
Authors: Thongchote Kanogwun , Chinwaro Usa , Lapmanee Sarawut
Published: August 2024

Background The postural abnormality, forward shoulder posture (FSP), is the most common cause of respiratory impairment in older individuals with chronic obstructive pulmonary disease (COPD). A recent study found that performing pectoral stretching and scapular strengthening exercises for eight weeks could reduce FSP in healthy participants. We aimed to determine the effects of pectoral stretching and scapular stabilizer strengthening exercises on FSP, chest wall mobility, respiratory muscle strength, and pulmonary function in male patients with COPD. Methods This study was randomized clinical trial. Forty male COPD patients with FSP aged 60–90 years were included and randomly allocated to control (n=20) and exercise (n=20) groups. Following completion of the scapulothoracic exercises (three days/week, for eight weeks), respiratory functions were assessed by measuring the magnitude of FSP, chest mobility, respiratory muscle strength, and pulmonary functions. Results FSP and thoracic kyphosis angle significantly decreased compared to controls (p<0.001, p<0.001). Middle and lower chest mobility markedly increased (p<0.001, p<0.001) and the pectoralis minor index significantly improved (p<0.001). The strength of the lower trapezius and serratus anterior muscles significantly increased at week eight of the exercise training (p<0.003, p<0.001). There was a marked increase in maximum inspiratory pressure and maximum expiratory pressure (p<0.001, p<0.001). Conclusions The eight-week combined pectoral muscles self-stretching and serratus anterior and lower trapezius strengthening exercises could be an effective treatment and/or prevention strategy for FSP reduction, leading to improved respiratory function in male COPD patients.
A survey of water chemistry used in zebrafish facilities and their effects on early zebrafish development
Authors: Porteus Cosima S. , Waples Ella , Dempsey Anna , Paull Gregory , Wilson Rod W.
Published: August 2024

Background There are a variety of published standard methods and water chemistry recommendations for zebrafish (Danio rerio) husbandry, but empirical evidence for their justification is often lacking, as is information on some variables that have important biological effects on fish. Importantly, these different recommendations could contribute to variability in results and fish welfare between or within institutions. Methods Here we document the current range of water chemistry used by various research institutions around the world and report initial findings on their effects on the development and growth of zebrafish. Over 40 institutes responded to a survey that revealed a large variation in water chemistry used for zebrafish husbandry including differences in the set-points and acceptable ranges for temperature, pH and conductivity. In subsequent experiments, zebrafish (D. rerio, WIK) embryos/larvae exposed to a large range of salt concentrations (50μM to 10mM Na+ or 30 – 2500 μS/cm) and CO2 levels (400 – 8,000 μatm). Results Larvae exposed to the lowest salt concentration (5 μM Na+ or < 30μS/cm) had a slower response to touch and their swim bladders were not inflated. Larvae exposed to 5-100 μM Na+ were 5 % shorter in total body length than those exposed to higher salt concentrations (>100 μM Na+). Zebrafish embryo/larvae exposed to intermediate pCO2 values (~2000 μatm) were 1 to 3.5% longer than those exposed to either ambient (400 μatm) or higher (4000 μatm) pCO2, but pCO2 did not affect developmental endpoints up to 4 dpf. Conclusions Overall, we highlight the magnitude of variation in water chemistry used within zebrafish research and provide some empirical evidence to show that not all of these water conditions might be optimal for developing zebrafish and reproducibility of research, although further research is necessary to determine longer-term effects of water chemistry on older larvae, juveniles and adults.