bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention
Authors: Anwar Mai M. , Özkan Esra , Shomalizadeh Narges , Sapancı Selin , Özler Ceyda , Kesibi Judy , Gürsoy-Özdemir Yasemin
Published: January 2023

Alzheimer’s disease (AD) is a predominantly heterogeneous disease with a highly complex pathobiology. The presence of amyloid-beta (Aβ) depositions and the accumulation of hyperphosphorylated tau protein remain the characteristic hallmarks of AD. These hallmarks can be detected throughout the brain and other regions, including cerebrospinal fluid (CSF) and the spinal cord. Microglia cells, the brain-resident macrophage type of the brain, are implicated in maintaining healthy brain homeostasis. The localized administration of primary healthy microglia (PHM) is suggested to play a role in mitigating AD hallmark depositions and associated cognitive dysfunction. Carbenoxolone (CBX) is the most common gap junction blocker. It cannot effectively cross the blood–brain barrier (BBB) under systemic administration. Therefore, localized administration of CBX may be a recommended intervention against AD by acting as an antioxidant and anti-inflammatory agent. This study aims to determine whether the localized intracerebroventricular (ICV) administration of PHM and CBX may act as an effective therapeutic intervention for AD neuroinflammatory type. In addition, this study also aims to reveal whether detecting AD hallmarks in the spinal cord and CSF can be considered functional and effective during AD early diagnosis. Male albino rats were divided into four groups: control (group 1), lipopolysaccharide (LPS)-induced AD neuroinflammatory type (group 2), ICV injection of LPS + isolated PHM (group 3), and ICV injection of LPS + CBX (group 4). Morris water maze (MWM) was conducted to evaluate spatial working memory. The brain and spinal cord were isolated from each rat with the collection of CSF. Our findings demonstrate that the localized administration of PHM and CBX can act as promising therapeutic approaches against AD. Additionally, Aβ and tau toxic aggregates were detected in the spinal cord and the CSF of the induced AD model concomitant with the brain tissues. Overall, it is suggested that the ICV administration of PHM and CBX can restore normal brain functions and alleviate AD hallmark depositions. Detecting these depositions in the spinal cord and CSF may be considered in AD early diagnosis. As such, conducting clinical research is recommended to reveal the benefits of related therapeutic approaches compared with preclinical findings.
Efficacy of different acupuncture therapies on postherpetic neuralgia: A Bayesian network meta-analysis
Authors: Cui Yang , Zhou Xinyu , Li Quan , Wang Delong , Zhu Jiamin , Zeng Xiangxin , Han Qichen , Yang Rui , Xu Siyu , Zhang Dongxu , Meng Xiangyue , Zhang Shuo , Sun Zhongren , Yin Hongna
Published: January 2023

Background

Postherpetic neuralgia (PHN) is a common, complex, and refractory type of neuropathic pain. Several systematic reviews support the efficacy of acupuncture and related treatments for PHN. Nevertheless, the efficacy of various acupuncture-related treatments for PHN remains debatable.

Objective

We aimed to assess the efficacy and safety of acupuncture-related treatments for PHN, identify the most effective acupuncture-related treatments, and expound on the current inadequacies and prospects in the applications of acupuncture-related therapies.

Methods

We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, Google Scholar, four Chinese databases (China National Knowledge Infrastructure, China Biomedical, Chongqing VIP, and Wan Fang databases), clinical research registration platform (World Health Organization International Clinical Trial Registration platform, China Clinical Trial Registration Center) for relevant studies. We also examined previous meta-analyses; gray literature; and reference lists of the selected studies. We then evaluated the risk of bias in the included studies and performed a Bayesian multiple network meta-analysis.

Results

We included 29 randomized controlled trials comprising 1,973 patients, of which five studies showed a high risk of bias. The pairwise meta-analysis results revealed that the efficacy of all acupuncture-related treatments for pain relief related to PHN was significantly better than antiepileptics. The network meta-analysis results showed that pricking and cupping plus antiepileptics were the most effective treatment, followed by electroacupuncture (EA) plus antiepileptics for pain relief in patients with PHN. EA plus antiepileptics ranked the best regarding reduced Pittsburgh Sleep Quality Index (PSQI) and Self-Rating Depression Scale (SDS) scores in patients with PHN. No results were found regarding the total response rate or quality of life in this study. Acupuncture-related treatments showed a lower incidence of adverse events than that of antiepileptics.

Conclusion

Acupuncture-related therapies are potential treatment options for PHN and are safe. Pricking and cupping plus antiepileptics, are the most effective acupuncture-related techniques for pain relief, while EA plus antiepileptics is the best acupuncture-related technique for improving PHN-related insomnia and depression symptoms. However, owing to the limitations of this study, these conclusions should be cautiously interpreted, and future high-quality studies are needed.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226422, identifier CRD42021226422.
Chronic Δ9-tetrahydrocannabinol impact on plasticity, and differential activation requirement for CB1-dependent long-term depression in ventral tegmental area GABA neurons in adult versus young mice
Authors: Ostlund Isaac , Von Gunten Michael , Smith Calvin , Edwards Jeffrey G.
Published: January 2023

The ventral tegmental area (VTA) mediates incentive salience and reward prediction error through dopamine (DA) neurons that are regulated by local VTA GABA neurons. In young mice, VTA GABA cells exhibit a form of synaptic plasticity known as long-term depression (LTD) that is dependent on cannabinoid 1 (CB1) receptors preceded by metabotropic glutamate receptor 5 (mGluR5) signaling to induce endocannabinoid production. This LTD was eliminated following chronic (7–10 consecutive days) exposure to the marijuana derived cannabinoid Δ9 -tetrahydrocannabinol (THC). We now examine the mechanism behind THC-induced elimination of LTD in adolescents as well as plasticity induction ability in adult versus young male and female mice using whole-cell electrophysiology experiments of VTA GABA cells. Chronic THC injections in adolescents resulted in a loss of CB1 agonist-mediated depression, illustrating chronic THC likely desensitizes or removes synaptic CB1. We noted that seven days withdrawal from chronic THC restored LTD and CB1 agonist-induced depression, suggesting reversibility of THC-induced changes. Adult mice continue to express functional mGluR5 and CB1, but require a doubling of the synaptic stimulation compared to young mice to induce LTD, suggesting a quantitative difference in CB1-dependent plasticity between young and adult mice. One potential rationale for this difference is changes in AMPA and NMDA glutamate receptors. Indeed, AMPA/NMDA ratios were increased in in adults compared to young mice. Lastly, we performed quantitative reverse-transcription PCR and identified that CB1, DAGLα, and GluA1 levels increased following chronic THC exposure. Collectively, our data demonstrate the first age-dependent GABA neuron plasticity in the VTA, which could have implications for decreased THC dependence capacity in adults, as well as the mechanism behind chronic THC-induced synaptic alterations in young mice.
Learning channel-selective and aberrance repressed correlation filter with memory model for unmanned aerial vehicle object tracking
Authors: Cui Jianjie , Wu Jingwei , Zhao Liangyu
Published: January 2023

To ensure that computers can accomplish specific tasks intelligently and autonomously, it is common to introduce more knowledge into artificial intelligence (AI) technology as prior information, by imitating the structure and mindset of the human brain. Currently, unmanned aerial vehicle (UAV) tracking plays an important role in military and civilian fields. However, robust and accurate UAV tracking remains a demanding task, due to limited computing capability, unanticipated object appearance variations, and a volatile environment. In this paper, inspired by the memory mechanism and cognitive process in the human brain, and considering the computing resources of the platform, a novel tracking method based on Discriminative Correlation Filter (DCF) based trackers and memory model is proposed, by introducing dynamic feature-channel weight and aberrance repressed regularization into the loss function, and by adding an additional historical model retrieval module. Specifically, the feature-channel weight integrated into the spatial regularization (SR) enables the filter to select features. The aberrance repressed regularization provides potential interference information to the tracker and is advantageous in suppressing the aberrances caused by both background clutter and appearance changes of the target. By optimizing the aforementioned two jointly, the proposed tracker could restrain the potential distractors, and train a robust filter simultaneously by focusing on more reliable features. Furthermore, the overall loss function could be optimized with the Alternative Direction Method of Multipliers (ADMM) method, thereby improving the calculation efficiency of the algorithm. Meanwhile, with the historical model retrieval module, the tracker is encouraged to adopt some historical models of past video frames to update the tracker, and it is also incentivized to make full use of the historical information to construct a more reliable target appearance representation. By evaluating the method on two challenging UAV benchmarks, the results prove that this tracker shows superior performance compared with most other advanced tracking algorithms.
Sensory impairment and cognitive decline among older adults: An analysis of mediation and moderation effects of loneliness
Authors: Ge Shaoqing , Pan Wei , Wu Bei , Plassman Brenda L. , Dong XinQi , McConnell Eleanor S.
Published: January 2023

Background

Multiple studies have reported that hearing and vision impairment are linked to cognitive decline. Yet little is known about factors that may influence the association between sensory impairment and cognitive decline. This study examined if loneliness mediates or moderates the impact of sensory impairment on cognitive decline as individuals age.

Methods

This was a longitudinal study using data from the Health and Retirement Study (HRS) and The Aging, Demographics, and Memory Study (ADAMS) (N = 243). We used one timepoint of hearing and vision (ADAMS 2006–2008), one timepoint of loneliness (HRS 2006–2008), and five waves of cognition (HRS 2006–2014). Hearing impairment was defined by an inability to hear pure-tone stimuli of 25 dB at frequencies between 0.5 and 4.0 kHz in either ear. Visual impairment was defined as having corrected binocular vision worse than 20/40. Longitudinal parallel-process (LPP) analysis was conducted at a significance level of α = 0.05 (one-tailed).

Results

Loneliness moderated but did not mediate the association between visual impairment and the rate of cognitive decline (standardized β =−0.108, p < 0.05). No moderation or mediation effect of loneliness was found for the association between hearing impairment and cognitive decline. Both vision and hearing impairment were significantly associated with increased severity of loneliness.

Conclusion

Visual impairment combined with an elevated level of loneliness may produce a more synergistic, deleterious impact on older adults’ cognitive function than visual impairment alone. This study highlights the importance of promoting a healthy social and psychological status for older adults with sensory impairment.
GRIN2B-related neurodevelopmental disorder: current understanding of pathophysiological mechanisms
Authors: Sabo Shasta L. , Lahr Jessica M. , Offer Madelyn , Weekes Anika LA , Sceniak Michael P.
Published: January 2023

The GRIN2B-related neurodevelopmental disorder is a rare disease caused by mutations in the GRIN2B gene, which encodes the GluN2B subunit of NMDA receptors. Most individuals with GRIN2B-related neurodevelopmental disorder present with intellectual disability and developmental delay. Motor impairments, autism spectrum disorder, and epilepsy are also common. A large number of pathogenic de novo mutations have been identified in GRIN2B. However, it is not yet known how these variants lead to the clinical symptoms of the disease. Recent research has begun to address this issue. Here, we describe key experimental approaches that have been used to better understand the pathophysiology of this disease. We discuss the impact of several distinct pathogenic GRIN2B variants on NMDA receptor properties. We then critically review pivotal studies examining the synaptic and neurodevelopmental phenotypes observed when disease-associated GluN2B variants are expressed in neurons. These data provide compelling evidence that various GluN2B mutants interfere with neuronal differentiation, dendrite morphogenesis, synaptogenesis, and synaptic plasticity. Finally, we identify important open questions and considerations for future studies aimed at understanding this complex disease. Together, the existing data provide insight into the pathophysiological mechanisms that underlie GRIN2B-related neurodevelopmental disorder and emphasize the importance of comparing the effects of individual, disease-associated variants. Understanding the molecular, cellular and circuit phenotypes produced by a wide range of GRIN2B variants should lead to the identification of core neurodevelopmental phenotypes that characterize the disease and lead to its symptoms. This information could help guide the development and application of effective therapeutic strategies for treating individuals with GRIN2B-related neurodevelopmental disorder.
Comprehensive fruit quality assessment and identification of aroma-active compounds in green pepper (Capsicum annuum L.)
Authors: Zhang Jing , Wang Cheng , Wang Junwen , Yang Yan , Han Kangning , Bakpa Emily Patience , Li Jing , Lyu Jian , Yu Jihua , Xie Jianming
Published: January 2023

The wrinkled pepper (Capsicum annuum L.) is a type of chili pepper domesticated in northwestern China, with a characteristic flavor. Fifteen wrinkled and four smooth-skinned pepper varieties were evaluated for morphology, texture, color, nutrients, capsaicinoids, and volatile compounds at the mature fruit stage. The sensory evaluation showed wrinkled pepper was superior to smooth pepper in texture, and it has a highly significant correlation (p < 0.01) with cuticle thickness, maximum penetrating force, lignin content, and moisture content. Citric acid was the major organic acid in peppers, accounting for 39.10–63.55% of the total organic acids, followed by quininic acid. The average oxalic acid content of smooth peppers was 26.19% higher than that of wrinkled peppers. The pungency of wrinkled pepper fruits ranged from 1748.9 to 25529.4 SHU, which can be considered slightly to very spicy, while the four smooth varieties ranged between 866.63 and 8533.70 SHU, at slightly to moderately spicy. A total of 199 volatile compounds were detected in the 19 pepper varieties. The average volatile content of wrinkled pepper was 39.79% higher than that of smooth pepper. Twenty-nine volatile compounds, including 14 aldehydes, four alcohols, three esters, three ketones, two furans, one pyrazine, one acid, and one phenol, contributed to the fragrance of peppers and could be regarded as aroma-active compounds, with 2-isobutyl-3-methoxypyrazine being the major contributor among the 19 pepper varieties. Wrinkled pepper can be confidently distinguished from smooth pepper and is of superior quality. The current findings outlined the major texture-related characteristics of pepper as well as the main aroma-active compounds, providing valuable information for pepper quality breeding and consumer guidelines.
Birth outcomes, puberty onset, and obesity as long-term predictors of biological aging in young adulthood
Authors: Jáni Martin , Zacková Lenka , Piler Pavel , Andrýsková Lenka , Brázdil Milan , Marečková Klára
Published: January 2023

Background

Biological aging and particularly the deviations between biological and chronological age are better predictors of health than chronological age alone. However, the predictors of accelerated biological aging are not very well understood. The aim was to determine the role of birth outcomes, time of puberty onset, body mass index (BMI), and body fat in accelerated biological aging in the third decade of life.

Methods

We have conducted a second follow-up of the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) prenatal birth cohort in young adulthood (52% male; age 28–30; n = 262) to determine the role of birth outcomes, pubertal timing, BMI, and body fat on biological aging. Birth outcomes included birth weight, length, and gestational age at birth. Pubertal timing was determined by the presence of secondary sexual characteristics at the age of 11 and the age of first menarche in women. Biological age was estimated using the Klemera-Doubal Method (KDM), which applies 9-biomarker algorithm including forced expiratory volume in one second (FEV1), systolic blood pressure, glycated hemoglobin, total cholesterol, C-reactive protein, creatinine, urea nitrogen, albumin, and alkaline phosphatase. Accelerated/decelerated aging was determined as the difference between biological and chronological age (BioAGE).

Results

The deviations between biological and chronological age in young adulthood ranged from −2.84 to 4.39 years. Accelerated biological aging was predicted by higher BMI [in both early (R2adj = 0.05) and late 20s (R2adj = 0.22)], subcutaneous (R2adj = 0.21) and visceral fat (R2adj = 0.25), puberty onset (ηp2 = 0.07), birth length (R2adj = 0.03), and the increase of BMI over the 5-year period between the two follow-ups in young adulthood (R2adj = 0.09). Single hierarchical model revealed that shorter birth length, early puberty onset, and greater levels of visceral fat were the main predictors, together explaining 21% of variance in accelerated biological aging.

Conclusion

Our findings provide comprehensive support of the Life History Theory, suggesting that early life adversity might trigger accelerated aging, which leads to earlier onset of puberty but decreasing fitness in adulthood, reflected by more visceral fat and higher BMI. Our findings also suggest that reduction of BMI in young adulthood slows down biological aging.
Case report: Acquired neurotrophic tyrosine receptor kinase inhibitor resistance in a patient with pancreatic neuroendocrine carcinoma receiving entrectinib
Authors: Wu Wen-Chi , Chen Ming-Huang
Published: January 2023

Pancreatic neuroendocrine carcinoma (panNEC) is a rare disease. The rearrangements of neurotrophic tropomyosin receptor kinase (NTRK) genes are oncogenic. And in the existed literatures, the prevalence of NTRK3 was only 0.1% in neuroendocrine tumors. NTRK inhibitor was approved for refractory and recurrence NTRK fusion-positive solid tumors did not respond to standard treatment. We described a patient with panNEC who was confirmed to have ETV6-NTRK3 fusion gene by liquid biopsy. The patient initially responded well to entrectinib, a first-generation NTRK inhibitor, but developed resistance with two acquired NTRK3-G623R and NTRK3-G623E mutations detected by a second liquid biopsy. Kirsten rat sarcoma vial oncogene (KRAS) K117N mutation was found initially but became undetectable after resistance. This was the first report demonstrating the novel agent, entrectinib, used for the NTRK3-fusion gene found by the liquid biopsy in panNEC. Our report provides evidence of not only the effectiveness but also the acquired resistance of entrectinib. Also, we highlighted the potential role of genomic sequencing after entrectinib failure. Furthermore, liquid biopsy should be considered if acquiring tissue from the patient is challenging. Further studies regarding NTRK inhibitors in panNEC were needed.
Case report: Clinical highlights and radiological classification of IgG4-related spinal pachymeningitis: A rare case series and updated review of the literature
Authors: Yang Fan , Liu Zhengang , Zhang Yibo , Li Pengfu , Zhu Yuhang , Zhu Qingsan , Zhang Boyin
Published: January 2023

Purpose

Hypertrophic pachymeningitis associated with immunoglobulin G4-related disease (IgG4-RD) has been rarely reported, and there is little information and no clear consensus on the management of IgG4-related spinal pachymeningitis (IgG4-RSP). The present study described its possible clinical features, including the symptoms, imaging, treatment and prognosis of patients with IgG4-RSP.

Methods

We report three patients who presented with progressive neurological dysfunction due to spinal cord compression. Relevant articles were searched from the PubMed, Web of Science, and Embase databases, and the resulting literature was reviewed.

Results

The literature review provided a summary of 45 available cases, which included three cases from our center. Progressive worsening of neurological impairment was observed in 22 patients (48.9%). The lesions involved the thoracic spine (n=28, 62.2%), cervical spine (n=26, 57.8%), lumbar spine (n=9, 20.0%), and sacral spine (n=1, 2.2%). Furthermore, the lesions were located in the dura mater (n=18, 40.0%), epidural space (n=17, 37.8%), intradural-extramedullary space (n=9, 20.0%), and intramedullary space (n=1, 2.2%). On magnetic resonance imaging (MRI), the lesions generally appeared as striated, fusiform, or less often lobulated oval changes, with homogeneous (n=17,44.7%) and dorsal (n=15,39.5%) patterns being the most common. Thirty-five patients had homogeneous T1 gadolinium enhancement. Early surgical decompression, corticosteroid treatment, and steroid-sparing agents offered significant therapeutic advantages. A good therapeutic response to disease recurrence was observed with the medication.

Conclusion

The number of reported cases of IgG4-RSP remains limited, and patients often have progressive worsening of their neurological symptoms. The features of masses identified on the MRI should be considered. The prognosis was better with decompression surgery combined with immunosuppressive therapy. Long-term corticosteroid treatment and steroid-sparing agent maintenance therapy should be ensured. A systemic examination is recommended to identify the presence of other pathologies.
CircCCDC66: Emerging roles and potential clinical values in malignant tumors
Authors: Wang Xiaoxiao , Zhang Chao , Song Huangqin , Yuan Junlong , Zhang Lei , He Jiefeng
Published: January 2023

Circular RNAs (circRNAs) are endogenous non-coding RNAs (ncRNAs) with a closed-loop structure. In recent years, circRNAs have become the focus of much research into RNA. CircCCDC66 has been identified as a novel oncogenic circRNA and is up-regulated in a variety of malignant tumors including thyroid cancer, non-small cell carcinoma, gastric cancer, colorectal cancer, renal cancer, cervical cancer, glioma, and osteosarcoma. It mediates cancer progression by regulating epigenetic modifications, variable splicing, transcription, and protein translation. The oncogenicity of circCCDC66 suppresses or promotes the expression of related genes mainly through direct or indirect pathways. This finding suggests that circCCDC66 is a biomarker for cancer diagnosis, prognosis assessment and treatment. However, there is no review on the relationship between circCCDC66 and cancers. Thus, the expression, biological functions, and regulatory mechanisms of circCCDC66 in malignant tumor and non-tumor diseases are summarized. The clinical value and prognostic significance of circCCDC66 are also evaluated, which can provide insights helpful to those exploring new strategies for the early diagnosis and targeted treatment of malignancies.
Response and resistance to BRAFV600E inhibition in gliomas: Roadblocks ahead?
Authors: Capogiri Monica , De Micheli Andrea J. , Lassaletta Alvaro , Muñoz Denise P. , Coppé Jean-Philippe , Mueller Sabine , Guerreiro Stucklin Ana S.
Published: January 2023

BRAFV600E represents the most common BRAF mutation in all human cancers. Among central nervous system (CNS) tumors, BRAFV600E is mostly found in pediatric low-grade gliomas (pLGG, ~20%) and, less frequently, in pediatric high-grade gliomas (pHGG, 5-15%) and adult glioblastomas (GBM, ~5%). The integration of BRAF inhibitors (BRAFi) in the treatment of patients with gliomas brought a paradigm shift to clinical care. However, not all patients benefit from treatment due to intrinsic or acquired resistance to BRAF inhibition. Defining predictors of response, as well as developing strategies to prevent resistance to BRAFi and overcome post-BRAFi tumor progression/rebound growth are some of the main challenges at present in the field. In this review, we outline current achievements and limitations of BRAF inhibition in gliomas, with a special focus on potential mechanisms of resistance. We discuss future directions of targeted therapy for BRAFV600E mutated gliomas, highlighting how insights into resistance to BRAFi could be leveraged to improve outcomes.
Comprehensive analysis of alfa defensin expression and prognosis in human colorectal cancer
Authors: Zhao Xinliang , Lu Mengnan , Liu Zhigang , Zhang Mingming , Yuan Hongmei , Dan Zhaoqiang , Wang Daihua , Ma Bingbing , Yang Yanqi , Yang Funing , Sun Ruifang , Li Lin , Dang Chengxue
Published: January 2023

Introduction

Colorectal cancer (CRC) is a serious threat to human health. Screening new biomarkers can provide basis for improving the prognosis and individualized treatment of CRC. Although some members of the defensin family were found increased in pancreatic cancer and CRC, their exact function and clinical significance remain unclear.

Methods

In this study, the expression, correlation, mutation, and functional enrichment of several defensin family members in pancreatic cancer and CRC were analyzed using tumor public databases and verified in several patients.

Results

Results showed no significant correlation between the expression levels of DEFA1-4 and CRC. The expression levels of DEFA5 and DEFA6 significantly increased in CRC tissues compared with those in normal tissues. DEFA5 may be associated with better prognosis of CRC, while DEFA6 may be associated with poor prognosis. Immunohistochemistry (IHC) experiments showed that the expression of DEFA6 was significantly higher in adenoma than in normal mucosa and slightly higher in carcinoma than in normal mucosa. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that DEFAs were closely related to hsa05202: transcriptional misregulation in cancer and Hsa04015: Rap1 signaling pathway. DEFA5 may be a stable and good prognostic marker, and DEFA6 may be a poor prognostic marker in CRC of metastasis.

Conclusion

Overall, DEFA5 and DEFA6 have a certain degree of sensitivity and specificity in predicting CRC.
Recent advances in the roles of exosomal microRNAs in neuroblastoma
Authors: Bhavsar Swapnil Parashram
Published: January 2023

Exosomal miRNAs (exo-miRs), universally found in biofluids, tissues, and/or conditioned medium of the cell cultures play a significant role in cell - cell communication, thus driving cancer progression and metastasis. Very few studies have explored the role of exo-miRs in the progression of children’s cancer - neuroblastoma. In this mini review, I briefly summarize the existing literature on the role of exo-miRs in the pathogenesis of neuroblastoma.
The Pain Medicine Curriculum Framework-structured integration of pain medicine education into the medical curriculum
Authors: Shipton Elspeth , Steketee Carole , Visser Eric
Published: January 2023

Medical practitioners play an essential role in preventing pain, conducting comprehensive pain assessments, as well as promoting evidence-based practices. There is a need for the development of innovative, interprofessional and integrated pain medicine curricula for medical students. The Pain Medicine Curriculum Framework (PMCF) was developed to conceptualise a purposeful approach to the complex process of curriculum change and to prioritise the actions needed to address the gaps in pain medicine education. The PMCF comprises four dimensions: (1) future healthcare practice needs; (2) competencies and capabilities required of graduates; (3) teaching, learning and assessment methods; and (4) institutional parameters. Curricula need to meet the requirements of registration and accreditation bodies, but also equip graduates to serve in their particular local health system while maintaining the fundamental standards and values of these institutions. The curriculum needs to connect knowledge with experience and practice to be responsive to the changing needs of the increasingly complex health system yet adaptable to patients with pain in the local context. Appropriate learning, teaching and assessment strategies are necessary to ensure that medical practitioners of the future develop the required knowledge, skills and attitudes to treat the diverse needs of patients' experiencing pain. The historical, political, social and organisational values of the educational institution will have a significant impact on curriculum design. A more formalised approach to the development and delivery of a comprehensive pain medicine curriculum is necessary to ensure that medical students are adequately prepared for their future workplace responsibilities.
Does physiological-based cord clamping improve cerebral tissue oxygenation and perfusion in healthy term neonates? – A randomized controlled trial
Authors: Schwaberger Bernhard , Ribitsch Mirjam , Pichler Gerhard , Krainer Marlies , Avian Alexander , Baik-Schneditz Nariae , Ziehenberger Evelyn , Mileder Lukas Peter , Martensen Johann , Mattersberger Christian , Wolfsberger Christina Helene , Urlesberger Berndt
Published: January 2023

Objectives

To evaluate cerebral tissue oxygenation index (cTOI) during neonatal transition in a group of healthy full-term neonates receiving either a physiological-based approach of deferred cord clamping (CC) after the onset of stable regular breathing (PBCC group) or a standard approach of time-based CC < 1 min (control group). Secondary aim was to evaluate changes in cerebral blood volume (ΔCBV), peripheral arterial oxygen saturation (SpO2) and heart rate (HR) in those neonates.

Materials and Methods

We conducted a randomized controlled trial (clinicaltrials.gov: NCT02763436) including vaginally delivered healthy full-term neonates. Continuous measurements of cTOI and ΔCBV using near-infrared spectroscopy, and of SpO2 and HR using pulse oximetry were performed within the first 15 min after birth. Data of each minute of the PBCC group were compared to those of the control group.

Results

A total of 71 full-term neonates (PBCC: n = 35, control: n = 36) with a mean (SD) gestational age of 40.0 (1.0) weeks and a birth weight of 3,479 (424) grams were included. Median (IQR) time of CC was 275 (197–345) seconds and 58 (35–86) seconds in the PBCC and control group, respectively (p < 0.001). There were no significant differences between the two groups regarding cTOI (p = 0.319), ΔCBV (p = 0.814), SpO2 (p = 0.322) and HR (p = 0.878) during the first 15 min after birth.

Conclusion

There were no significant differences in the course of cTOI as well as ΔCBV, SpO2 and HR during the first 15 min after birth in a group of healthy full-term neonates, who received either deferred CC after the onset of stable regular breathing or standard CC < 1 min. Thus, deferring CC ≥ 1 min following a physiological-based approach offers no benefits regarding cerebral tissue oxygenation and perfusion after uncomplicated vaginal delivery compared to a time-based CC approach.
Low total cholesterol predicts early death in children with hemophagocytic lymphohistiocytosis
Authors: Xiao Li , Xu Ximing , Zhang Zhiling , Dou Ying , Guan Xianmin , Guo Yuxia , Yu Jie
Published: January 2023

Background

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and potentially life-threatening disorder. Identifying risk factors and timely adjustment of the given treatment regimens is critical to reducing the early mortality in HLH patients. Hypocholesterolemia has been reported to be associated with poor prognosis in a variety of critical illnesses. However, serum cholesterol is rarely studied in HLH patients, and its prognostic value is unclear.

Methods

We conducted a retrospective cohort study in National Clinical Research Center for Child Health and Disorders (Chongqing), identifying pediatric HLH patients (including genetically confirmed pHLH and not genetically confirmed pHLH) diagnosed with the HLH-2004 protocol and treated with immunochemotherapy between January 2008 and December 2020. The patients' blood lipid levels at initial diagnosis of HLH, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), were reviewed based on electronic medical records. Both Cox and logistic regression models were used to estimate the effects of blood lipid indicators on early death (within 30 days after diagnosis).

Results

A total of 353 patients were enrolled in the study, with a median age at diagnosis of 45 months. The observed 30-day mortality rate was 19.05% (64/336, 17 were lost to follow-up) and Kaplan-Meier-estimated 3-year survival rate was 61.67% (95% CI, 56.27%–67.59%). DNA-targeted sequencing of HLH-related genes was performed in 173 (49.0%, 173/353) patients (not all patients with suspected pHLH underwent genetic testing), and 29 patients were diagnosed with genetically confirmed pHLH. Lipid panel was performed in 349 patients: 91.98% (321/349) had TG ≥ 1.80 mmol/L, 62.75%(219/349) had TG ≥ 3.00 mmol/L, 92.84% (324/349) had HDL-C ≤ 1.04 mmol/L, 58.74% (205/349) had LDL-C ≤ 1.30 mmol/L and 24.64% (86/349) had TC ≤ 3.11 mmol/L. TC ≤ 3.11 mmol/L and BUN ≥ 7.14 mmol/L were the independent risk factors for 30-day mortality [HR(95%CI): 2.85(1.46, 5.57) and 2.90(1.48, 5.68), respectively]. The presence of one of these risk factors increased the 30-day mortality rate by 6-fold [HR = 6.24, 95%CI: (3.18, 12.22)] and the presence of two risk factors by nearly 10-fold [HR = 9.98, 95%CI: (4.23, 23.56)] compared with the patients with no risk factors.

Conclusion

Severe derangement of lipoproteins is common in children with HLH, and decreased TC is an independent risk factor for early death. Hypocholesterolemia should be included as a biomarker during the diagnosis and management of HLH patients.
Evaluation of presepsin as a diagnostic tool in newborns with risk of early-onset neonatal sepsis
Authors: Pospisilova Iva , Brodska Helena L. , Bloomfield Marketa , Borecka Klara , Janota Jan
Published: January 2023

Objectives

To evaluate the efficacy of presepsin (P-SEP) as a potential biomarker of early-onset neonatal sepsis (EOS) and compare it to other routinely used markers of inflammation. To establish the cut-off values of P-SEP for EOS.

Study design

184 newborns were prospectively recruited between January 2018 to December 2020. Newborns >34th gestational week with suspected infection were included up to 72 h after delivery, and divided into three categories (i.e., unlikely, possible, and probable infection) based on risk factors, clinical symptoms and laboratory results. Values of plasma P-SEP were sequentially analyzed.

Results

Median values of P-SEP in newborns with probable infection were significantly higher compared to healthy newborns (p = 0.0000013) and unlikely infection group (p = 0.0000025). The AUC for discriminating the probable infection group from the unlikely infection group was 0.845 (95% Cl: 0.708–0.921). The diagnostic efficacy of P-SEP was highest when used in combination with IL-6 and CRP (0.97; 95% CI: 0.911–0.990). The optimal cut-off value of P-SEP was determined to be 695 ng/L.

Conclusion

P-SEP, when combined with IL-6 and CRP, may be utilized as a negative predictive marker of EOS (NPV 97.2%, 95% CI: 93.3–101), especially in newborns at low to medium risk of infection.
Factors associated with follow-up care after pediatric concussion: A longitudinal population-based study in Alberta, Canada
Authors: Wittevrongel Krystle , Barrett Olesya , Hagel Brent E. , Schneider Kathryn J. , Johnson David W. , Yeates Keith Owen , Zwicker Jennifer D.
Published: January 2023

Background

Concussion is a common injury in children and adolescents. Current best practice guidelines indicate that recovery should be supervised through recurrent follow-up visits. A more detailed understanding of the system-level and individual factors that are associated with follow-up care is a critical step towards increasing evidence-based practice. The objective of this study was to identify predisposing, enabling, and need-based factors associated with follow-up care after pediatric concussion.

Materials and methods

A retrospective population-based cohort study was conducted using linked, province-wide administrative health data for all patients <18 years of age with a diagnosis of concussion, other specified injuries of the head, unspecified injury of head, or post-concussion syndrome (PCS) between April 1, 2004 and March 31, 2018 in Alberta, Canada. The association between predisposing, enabling, and need-based factors and the receipt of follow-up care within a defined episode of care (EOC) was analyzed using logistic regression models for the entire cohort and for EOC that began with a concussion diagnosis. Predisposing factors included age and sex. Enabling factors included the community type of patient residence, area-based socioeconomic status (SES), and visit year. Need-based factors included where the EOC began (outpatient vs. emergency settings) and history of previous concussion-related EOC.

Results

194,081 EOCs occurred during the study period but only 13% involved follow-up care (n = 25,461). Males and adolescents were more likely to receive follow-up care. Follow-up was less likely among patients who lived in remote communities or in areas of lower SES, while EOCs beginning in 2011 or later were more likely to involve follow-up care. Patients whose EOC began in outpatient settings, had more than one EOC, or a diagnosis of concussion were more likely to receive follow-up care.

Conclusion

Follow-up care for pediatric concussion has increased over time and is associated with patient age and sex, history of concussion-related EOC, where a patient lives (community type and area-based SES), and when and where the index visit occurs. A better understanding of which children are more likely to receive follow-up care, as well as how and when they do, is an important step in aligning practice with follow-up guidelines.
Applicability of vancomycin, meropenem, and linezolid in capillary microsamples vs. dried blood spots: A pilot study for microsampling in critically ill children
Authors: Xiaoyong Xu , Jinglin Wang , Guangfei Wang , Huimin Zhang , Hong Xu , Zhiping Li
Published: January 2023

Introduction

Therapeutic drug monitoring (TDM) has been shown to be clinically beneficial for critically ill patients. However, this is a burden for neonates or children with small circulating blood volumes. Here, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem, and linezolid.

Methods

Paired DBS and CMS samples were obtained from an intensive care unit (ICU) to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland-Altman difference plots.

Results

The microsampling methods validation showed excellent reliability and compatibility with the analysis of the sample matrix and hematocrit range of the studied population. The DBS and CMS accuracy and precision results were within accepted ranges and samples were stable at room temperature for at least 2 days and 8 h, respectively. Hematocrit had no impact on CMS, but sightly impacted DBS measurements. The CMS and DBS antibiotic concentrations correlated well (r > 0.98). The drug concentration ratio in DBS samples to that in CMS was 1.39 for vancomycin, 1.34 for meropenem, and 0.94 for linezolid. The EPC calculated from the DBS using individual hematocrit ranges presented comparable absolute values for vancomycin (slope: 1.06) and meropenem (slope: 1.04), with a mean of 98% and 99% of the measured CMS concentrations, respectively.

Discussion

This study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.
Persistent dyselectrolytemia in a neonate induced by liposomal amphotericin B. A case report
Authors: Puertas Sanjuan Adrian , Parramón-Teixidó Carlos Javier , Hernandez-Perez Susana , Frick Marie Antoinette , Cabañas Poy Maria Jose
Published: January 2023

Background

Nephrotoxicity is the most frequent serious adverse effect associated with amphotericin B deoxycholate treatment, for this reason, in recent years it has been relegated from routine clinical practice and replaced by the new liposomal formulations that have less nephrotoxicity. Nevertheless, dyselectrolytemia are a frequent adverse effect of the use of liposomal amphotericin B that usually are resolved with the withdrawal of the drug.

Case presentation

We present a preterm neonate of 25 weeks gestation, with preserved renal function and most electrolytes within normal limits for gestational age except for mild hyponatremia in the first month of life. Due to an infection of the central nervous system and growth of Candida albicans, he required treatment with endovenous liposomal amphotericin B as well as intrathecal amphotericin B deoxycholate showing severe hydroelectrolyte disturbances and clinical worsening compatible with possible tubulopathy showing hypokalemia and severe hyponatremia a few days after starting treatment that persisted over time even after withdrawal of both drugs. Subsequently to the main alterations described, hypomagnesemia, hypophosphatemia, glycosuria and tubular proteinuria were also observed. Calcium levels remained stable after amphotericin B administration and did not require supplementation. In preterm or low birth weight newborns who present unjustified, severe and difficult to correct hydroelectrolyte disturbances despite the usual treatment, a possible tubulopathy should be considered, whether hereditary, primary or secondary to toxins or drugs.

What Is New and Conclusion

We present the first case reported in a neonate in whom dyselectrolithemia has been maintained over time after withdrawal of liposomal amphotericin B.
Use of lung ultrasound in school-aged children with wheezing
Authors: Attanasi Marina , Sferrazza Papa Simone , Porreca Annamaria , Sferrazza Papa Giuseppe F. , Di Filippo Paola , Piloni Francesca , Dodi Giulia , Sansone Francesco , Di Pillo Sabrina , Chiarelli Francesco
Published: January 2023

Background

There is limited information available on fast and safe bedside tools that could help clinicians establish whether the pathological process underlying cases of wheezing is due to asthmatic exacerbation, asthmatic bronchitis, or pneumonia. The study's aim was to characterize Lung Ultrasound (LUS) in school-aged children with wheezing and evaluate its use for their follow-up treatment.

Materials and methods

We carried out a cross-sectional study involving 68 consecutive outpatients (mean age 9.9 years) with wheezing and suggestive signs of an acute respiratory infection. An expert sonographer, blinded to all subject characteristics, clinical course, and the study pediatrician's diagnosis, performed an LUS after spirometry and before BDT. The severity of acute respiratory symptoms was determined using the Pediatric Respiratory Assessment Measure (PRAM) score.

Results

The LUS was positive in 38.2% (26/68) of patients [12 (46.1%) with multiple B-lines, 24 (92.3%) with consolidation, and 22 (84.6%) with pleural abnormalities]. In patients with pneumonia, asthmatic bronchitis, and asthma, the percentages of those patients with a positive LUS were 100%, 57.7%, and 0%, respectively. Of note, patients with a positive LUS were associated with an increased need for hospital admission (30.8% vs. 2.4%, p = 0.001), administration of oxygen therapy (14.6% vs. 0%, p = 0.009), oral corticosteroids (84.6% vs. 19.0%, p < 0.001), and antibiotics (88.5% vs. 11.9%, p < 0.001); and a higher median value of PRAM score (4.0 (2.0–7.0) vs. 2.0 (1.0–5.0); p < 0.001).

Conclusions

Our findings would suggest the use of LUS as a safe and cheap tool used by clinicians to define the diagnosis of school-aged children with wheezing of unknown causes.
Predictive factors for rapid progression in preterm neonates with necrotizing enterocolitis
Authors: Chen Jiale , Zhong Weitao , Hou Longlong , Lin Tulian , Lyv Junjian , Tian Yan , Ma Zuyi , He Qiuming , Zhong Wei
Published: January 2023

Background

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency with significant mortality and morbidity rates. A subset of patients progressed rapidly and underwent surgical intervention within a short period. This study aimed to establish a model to predict the rapid progression of NEC in preterm neonates.

Methods

A retrospective study was conducted to review neonates with NEC between December 2015 and April 2019 at the Guangzhou Women and Children's Medical Center. Rapidly progressive NEC was defined as the need for surgical intervention or death within 48 h of NEC onset. Patients were divided into two groups: rapidly progressive NEC (RP-NEC) and non-rapidly progressive NEC (nRP-NEC). Data on demographics, perinatal characteristics, examination variables, and radiographic findings at onset were collected.

Results

A total of 216 preterm neonates with NEC were included in the study, of which 64 had RP-NEC and 152 had nRP-NEC. The mortality rates of patients with RP-NEC and nRP-NEC were 32.8% and 3.28%, respectively. Male sex (p-value, adjusted odds ratio [95% confidence interval]: 0.002, 3.43 [1.57, 7.53]), portal venous gas (0.000, 8.82 [3.73, 20.89]), neutrophils <2.0 × 109/L (0.005, 4.44 [1.59, 12.43]), pH <7.3 (7.2 ≤ pH < 7.3) (0.041, 2.95 [1.05, 8.31]), and pH <7.2 (0.000, 11.95 [2.97, 48.12]) at NEC onset were identified as independent risk factors for RP-NEC. An established model that included the four risk factors presented an area under the curve of 0.801 with 83% specificity and 66% sensitivity.

Conclusion

Among preterm neonates with NEC, a significantly higher mortality rate was observed in those with rapid progression. It is recommended that close surveillance be performed in these patients, and we are confident that our established model can efficiently predict this rapid progression course.