bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive tasks propagate the neural entrainment in response to a visual 40 Hz stimulation in humans
Authors: Khachatryan Elvira , Wittevrongel Benjamin , Reinartz Mariska , Dauwe Ine , Carrette Evelien , Meurs Alfred , Van Roost Dirk , Boon Paul , Van Hulle Marc M.
Published: October 2022

Introduction

Alzheimer's disease is one of the great challenges in the coming decades, and despite great efforts, a widely effective disease-modifying therapy in humans remains elusive. One particular promising non-pharmacological therapy that has received increased attention in recent years is based on the Gamma ENtrainment Using Sensory stimulation (GENUS), a high-frequency neural response elicited by a visual and/or auditory stimulus at 40 Hz. While this has shown to be effective in animal models, studies on human participants have reported varying success. The current work hypothesizes that the varying success in humans is due to differences in cognitive workload during the GENUS sessions.

Methods

We recruited a cohort of 15 participants who underwent a scalp-EEG recording as well as one epilepsy patient who was implanted with 50 subdural surface electrodes over temporo-occipital and temporo-basal cortex and 14 depth contacts that targeted the hippocampus and insula. All participants completed several GENUS sessions, in each of which a different cognitive task was performed.

Results

We found that the inclusion of a cognitive task during the GENUS session not only has a positive effect on the strength and extent of the gamma entrainment, but also promotes the propagation of gamma entrainment to additional neural areas including deep ones such as hippocampus which were not recruited when no cognitive task was required from the participants. The latter is of particular interest given that the hippocampal complex is considered to be one of the primary targets for AD therapies.

Discussion

This work introduces a possible improvement strategy for GENUS therapy that might contribute to increasing the efficacy of the therapy or shortening the time needed for the positive outcome.
Novel molecular mechanisms in Alzheimer’s disease: The potential role of DEK in disease pathogenesis
Authors: Greene Allie N. , Solomon Matia B. , Privette Vinnedge Lisa M.
Published: October 2022

Alzheimer’s disease and age-related dementias (AD/ADRD) are debilitating diseases that exact a significant physical, emotional, cognitive, and financial toll on the individual and their social network. While genetic risk factors for early-onset AD have been identified, the molecular and genetic drivers of late-onset AD, the most common subtype, remain a mystery. Current treatment options are limited for the 35 million people in the United States with AD/ADRD. Thus, it is critically important to identify novel molecular mechanisms of dementia-related pathology that may be targets for the development of new interventions. Here, we summarize the overarching concepts regarding AD/ADRD pathogenesis. Then, we highlight one potential molecular driver of AD/ADRD, the chromatin remodeling protein DEK. We discuss in vitro, in vivo, and ex vivo findings, from our group and others, that link DEK loss with the cellular, molecular, and behavioral signatures of AD/ADRD. These include associations between DEK loss and cellular and molecular hallmarks of AD/ADRD, including apoptosis, Tau expression, and Tau hyperphosphorylation. We also briefly discuss work that suggests sex-specific differences in the role of DEK in AD/ADRD pathogenesis. Finally, we discuss future directions for exploiting the DEK protein as a novel player and potential therapeutic target for the treatment of AD/ADRD.
Inhibiting amyloid beta (1–42) peptide-induced mitochondrial dysfunction prevents the degradation of synaptic proteins in the entorhinal cortex
Authors: Olajide Olayemi Joseph , La Rue Claudia , Bergdahl Andreas , Chapman Clifton Andrew
Published: October 2022

Increasing evidence suggests that mitochondrial dysfunction and aberrant release of mitochondrial reactive oxygen species (ROS) play crucial roles in early synaptic perturbations and neuropathology that drive memory deficits in Alzheimer’s disease (AD). We recently showed that solubilized human amyloid beta peptide 1–42 (hAβ1–42) causes rapid alterations at glutamatergic synapses in the entorhinal cortex (EC) through the activation of both GluN2A- and GluN2B-containing NMDA receptors. However, whether disruption of mitochondrial dynamics and increased ROS contributes to mechanisms mediating hAβ1–42-induced synaptic perturbations in the EC is unknown. Here we assessed the impact of hAβ1–42 on mitochondrial respiratory functions, and the expression of key mitochondrial and synaptic proteins in the EC. Measurements of mitochondrial respiratory function in wild-type EC slices exposed to 1 μM hAβ1–42 revealed marked reductions in tissue oxygen consumption and energy production efficiency relative to control. hAβ1–42 also markedly reduced the immunoexpression of both mitochondrial superoxide dismutase (SOD2) and mitochondrial-cytochrome c protein but had no significant impact on cytosolic-cytochrome c expression, voltage-dependent anion channel protein (a marker for mitochondrial density/integrity), and the immunoexpression of protein markers for all five mitochondrial complexes. The rapid impairments in mitochondrial functions induced by hAβ1–42 were accompanied by reductions in the presynaptic marker synaptophysin, postsynaptic density protein (PSD95), and the vesicular acetylcholine transporter, with no significant changes in the degradative enzyme acetylcholinesterase. We then assessed whether reducing hAβ1–42-induced increases in ROS could prevent dysregulation of entorhinal synaptic proteins, and found that synaptic impairments induced by hAβ1–42 were prevented by the mitochondria-targeted antioxidant drug mitoquinone mesylate, and by the SOD and catalase mimetic EUK134. These findings indicate that hAβ1–2 can rapidly disrupt mitochondrial functions and increase ROS in the entorhinal, and that this may contribute to synaptic dysfunctions that may promote early AD-related neuropathology.
Emotional scene remembering: A combination of disturbing and facilitating effects of emotion?
Authors: Bouvarel David , Gardette Jeremy , Saint-Macary Manon , Hot Pascal
Published: October 2022

An emotion-induced memory trade-off effect is frequently reported when participants have to memorize complex items that include both neutral and emotional features. This bias corresponds to better remembering of central emotional information accompanied by poor performance related to neutral background information. Although the trade-off effect has been mainly associated with attentional bias toward emotional content, findings suggest that other non-attentional cognitive processes could also be involved. The aim of this work was to assess whether emotional effects would be reported apart from their influence on attentional processing in an immediate delay memory task. Three studies were conducted. In Study 1, manipulation of the diffusion quality of emotional content allowed us to select focal emotional pictures vs. diffuse emotional pictures, which prevented attentional focus. The two studies that followed consisted of a recognition task of low- and high-complexity pictures in which we used partial visual cues during the test that could display either the emotional elements (i.e., central patch cues, Study 2) or the peripheral elements (i.e., peripheral patch cues, Study 3) of the focal emotional pictures. Results from Studies 2 and 3 replicated traditional trade-off effects only for high-complexity pictures. In addition, diffuse emotional pictures were associated with lower memory performance than were neutral pictures, suggesting that emotion features could both disturb and enhance (via their attentional effect) encoding processes.
Exploring surface electromyography (EMG) as a feedback variable for the human-in-the-loop optimization of lower limb wearable robotics
Authors: Grimmer Martin , Zeiss Julian , Weigand Florian , Zhao Guoping
Published: October 2022

Human-in-the-loop (HITL) optimization with metabolic cost feedback has been proposed to reduce walking effort with wearable robotics. This study investigates if lower limb surface electromyography (EMG) could be an alternative feedback variable to overcome time-intensive metabolic cost based exploration. For application, it should be possible to distinguish conditions with different walking efforts based on the EMG. To obtain such EMG data, a laboratory experiment was designed to elicit changes in the effort by loading and unloading pairs of weights (in total 2, 4, and 8 kg) in three randomized weight sessions for 13 subjects during treadmill walking. EMG of seven lower limb muscles was recorded for both limbs. Mean absolute values of each stride prior to and following weight loading and unloading were used to determine the detection rate (100% if every loading and unloading is detected accordingly) for changing between loaded and unloaded conditions. We assessed the use of multiple consecutive strides and the combination of muscles to improve the detection rate and estimated the related acquisition times of diminishing returns. To conclude on possible limitations of EMG for HITL optimization, EMG drift was evaluated during the Warmup and the experiment. Detection rates highly increased for the combination of multiple consecutive strides and the combination of multiple muscles. EMG drift was largest during Warmup and at the beginning of each weight session. The results suggest using EMG feedback of multiple involved muscles and from at least 10 consecutive strides (5.5 s) to benefit from the increases in detection rate in HITL optimization. In combination with up to 20 excluded acclimatization strides, after changing the assistance condition, we advise exploring about 16.5 s of walking to obtain reliable EMG-based feedback. To minimize the negative impact of EMG drift on the detection rate, at least 6 min of Warmup should be performed and breaks during the optimization should be avoided. Future studies should investigate additional feedback variables based on EMG, methods to reduce their variability and drift, and should apply the outcomes in HITL optimization with lower limb wearable robots.
Probing the structure and function of locus coeruleus projections to CNS motor centers
Authors: Waterhouse Barry D. , Predale Haven K. , Plummer Nicholas W. , Jensen Patricia , Chandler Daniel J.
Published: October 2022

The brainstem nucleus locus coeruleus (LC) sends projections to the forebrain, brainstem, cerebellum and spinal cord and is a source of the neurotransmitter norepinephrine (NE) in these areas. For more than 50 years, LC was considered to be homogeneous in structure and function such that NE would be released uniformly and act simultaneously on the cells and circuits that receive LC projections. However, recent studies have provided evidence that LC is modular in design, with segregated output channels and the potential for differential release and action of NE in its projection fields. These new findings have prompted a radical shift in our thinking about LC operations and demand revision of theoretical constructs regarding impact of the LC-NE system on behavioral outcomes in health and disease. Within this context, a major gap in our knowledge is the relationship between the LC-NE system and CNS motor control centers. While we know much about the organization of the LC-NE system with respect to sensory and cognitive circuitries and the impact of LC output on sensory guided behaviors and executive function, much less is known about the role of the LC-NE pathway in motor network operations and movement control. As a starting point for closing this gap in understanding, we propose using an intersectional recombinase-based viral-genetic strategy TrAC (Tracing Axon Collaterals) as well as established ex vivo electrophysiological assays to characterize efferent connectivity and physiological attributes of mouse LC-motor network projection neurons. The novel hypothesis to be tested is that LC cells with projections to CNS motor centers are scattered throughout the rostral-caudal extent of the nucleus but collectively display a common set of electrophysiological properties. Additionally, we expect to find these LC projection neurons maintain an organized network of axon collaterals capable of supporting selective, synchronous release of NE in motor circuitries for the purpose of coordinately regulating operations across networks that are responsible for balance and movement dynamics. Investigation of this hypothesis will advance our knowledge of the role of the LC-NE system in motor control and provide a basis for treating movement disorders resulting from disease, injury, or normal aging.
Plasma anion gap and risk of in-hospital mortality in patients with spontaneous subarachnoid hemorrhage
Authors: Ji LinJin , Tong Xin , Wang KaiChun , Jiang ZhiQun , Liu Aihua
Published: October 2022

Background

The association between the serum anion gap (AG) and prognosis of patients with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Thus, this study aimed to explore the association between AG levels and mortality in patients with SAH in the intensive care unit (ICU).

Methods

This was a retrospective analysis of data stored in the Medical Information Mart for Intensive Care–IV and eICU Collaborative Research databases. Critically ill patients diagnosed with spontaneous SAH were included. The primary outcome measure was in-hospital all-cause mortality. A multivariate Cox proportional hazards regression model and a restricted cubic spline were used to evaluate the relationship between AG concentration and outcomes. Kaplan–Meier curves were used to compare cumulative survival among patients with AG levels.

Results

A total of 1,114 patients were enrolled. AG concentration was significantly associated with in-hospital all-cause mortality [hazard ratio ([HR], 1.076 (95% confidence interval (CI), 1.021–1.292; p = 0.006)]. The risk of mortality was higher in the Category 2 group (AG ≥10 mmol/L and <13 mmol/L; HR, 1.961; 95% CI, 1.157–3.324; p = 0.0) and the Category 3 group (AG ≥13 mmol/L; HR, 2.151; 95% CI, 1.198–3.864; p = 0.010) than in the Category 1 group (AG < 10 mmol/L). Cumulative survival rates were significantly lower in patients with higher AG levels (log-rank p < 0.001).

Conclusions

In-hospital and ICU mortalities increase with increasing AG concentration in patients with SAH. An increased serum AG level is an independent, significant, and robust predictor of all-cause mortality. Thus, serum AG levels may be used in the risk stratification of SAH.
High cerebrospinal fluid lactate concentration at 48 h of hospital admission predicts poor outcomes in patients with tuberculous meningitis: A multicenter retrospective cohort study
Authors: Liu Chenchao , Huai Ruixue , Xiang Yijia , Han Xu , Chen Zixiang , Liu Yuhan , Liu Xingjun , Liu Huiquan , Zhang Hong , Wang Sihan , Hao Lingyu , Bo Yin , Luo Yuanbo , Wang Yiyi , Wang Yi
Published: October 2022

Objective

This study aimed to analyze the cerebrospinal fluid (CSF) parameters affecting the outcomes of patients with tuberculous meningitis (TBM).

Methods

This is a multi-center, retrospective, cohort study involving 81 patients who were diagnosed with TBM and treated in Haihe Clinical College of Tianjin Medical University, Tianjin Medical University General Hospital, and General Hospital of Air Force PLA from January 2016 to December 2019. Baseline data, Glasgow Coma Scale (GCS) score, and clinical presentations of all patients were collected at admission. CSF samples were collected at 48 h, 1, 2, and 3 weeks after admission. CSF lactate, adenosine deaminase, chloride, protein, glucose levels and intracranial pressure were measured. After a follow-up of 16.14 ± 3.03 months, all patients were assessed using the modified Rankin Scale (mRS) and divided into good (mRS scores of 0–2 points) and poor outcome groups (mRS scores of 3–6 points). The differences in patients' baseline data, GCS score, clinical presentations, and levels of CSF parameters detected at 48 h, 1, 2, and 3 weeks after admission between two groups were compared. Statistically significant variables were added to the binary logistic regression model to identify the factors impacting the outcomes of patients with TBM. Receiver operating characteristic (ROC) curve was used to assess the predictive ability of the model.

Results

The CSF lactate level exhibited a decreasing trend within 3 weeks of admission in the two groups. For the within-group comparison, statistically significant differences in the lactate level was found in both groups between four different time points. A binary logistic regression model revealed that CSF lactate level at 48 h after admission, age, and GSC score on admission were independently associated with the outcomes of patients with TBM. ROC curve analysis showed that the area under the ROC curve (AUC) was 0.786 for the CSF lactate level (48 h), 0.814 for GCS score, and 0.764 for age.

Conclusion

High CSF lactate level at 48 h after admission is one of the important factors for poor outcomes in patients with TBM.
Supportive psychological therapy can effectively treat post-stroke post-traumatic stress disorder at the early stage
Authors: Jiang Che , Li Zhensheng , Du Chenggang , Zhang Xiwu , Chen Zhuang , Luo Gaoquan , Wu Xiaona , Wang Jiajia , Cai Yan , Zhao Gang , Bai Hongmin
Published: October 2022

Post-traumatic stress disorder (PTSD) can develop after stroke attacks, and its rate ranges from 4 to 37% in the stroke population. Suffering from PTSD not only decreases stroke patient’s quality of life, but also relates to their non-adherence of treatment. Since strokes often recur and progress, long-term medical management is especially important. However, previous studies generally focused on the epidemiological characteristics of post-stroke PTSD, while there are literally no studies on the psychological intervention. In our study, 170 patients with a first-ever stroke during the acute phase were recruited. They were randomized into Psycho-therapy group 1 and Control group 1, and were administered with preventive intervention for PTSD or routine health education, respectively. At 2-month follow-up, PTSD symptoms were evaluated. Participants who were diagnosed with post-stroke PTSD were further randomized into Psycho-therapy group 2 and Control group 2, and received supportive therapy or routine health counseling, respectively. At 6-month follow-up (1°month after the therapy was completed), PTSD symptoms were re-evaluated. Our results showed that at 2-month, the PTSD incidence in our series was 11.69%, and the severity of stroke was the only risk factor for PTSD development. The preventive intervention was not superior to routine health education for PTSD prevention. At 6-month, results indicated the supportive therapy did have a fine effect in ameliorating symptoms for diagnosed PTSD patients, superior to routine health counseling. Thus, our study was the first to provide evidence that the supportive therapy was effective in treating post-stroke PTSD early after its diagnosis. This clinical trial was preregistered on www.chictr.org.cn (ChiCTR2100048411).
Adaptive optics in single objective inclined light sheet microscopy enables three-dimensional localization microscopy in adult Drosophila brains
Authors: Hung Shih-Te , Llobet Rosell Arnau , Jurriens Daphne , Siemons Marijn , Soloviev Oleg , Kapitein Lukas C. , Grußmayer Kristin , Neukomm Lukas J. , Verhaegen Michel , Smith Carlas
Published: October 2022

Single-molecule localization microscopy (SMLM) enables the high-resolution visualization of organelle structures and the precise localization of individual proteins. However, the expected resolution is not achieved in tissue as the imaging conditions deteriorate. Sample-induced aberrations distort the point spread function (PSF), and high background fluorescence decreases the localization precision. Here, we synergistically combine sensorless adaptive optics (AO), in-situ 3D-PSF calibration, and a single-objective lens inclined light sheet microscope (SOLEIL), termed (AO-SOLEIL), to mitigate deep tissue-induced deteriorations. We apply AO-SOLEIL on several dSTORM samples including brains of adult Drosophila. We observed a 2x improvement in the estimated axial localization precision with respect to widefield without aberration correction while we used synergistic solution. AO-SOLEIL enhances the overall imaging resolution and further facilitates the visualization of sub-cellular structures in tissue.
High circadian stimulus lighting therapy for depression: Meta-analysis of clinical trials
Authors: Zhou Li , Hou Dandan , Wang Yang , Zhou Sicong , Lin Yandan
Published: October 2022

Although bright light therapy (BLT) has been widely used in the clinical treatment of depression, the antidepressant effect of BLT is not well understood. Considering the connection between depression and disrupted circadian rhythm, we assumed the model of human circadian phototransduction could be more accurate in evaluating the efficacy of BLT for depression compared to light level and spectrum. A systematic review and meta-analysis were conducted and the CS (circadian stimulus) model was used to quantify the efficacy of lighting in BLT. Articles published up to June 2022 were searched in COCHRANE, EMBASE, MEDLINE, and Web of Science. Randomized clinical trials included articles using high circadian stimulus (H-CS, CS > 0.1) as lighting therapy for people with depressive disorder vs. a control group (CS < 0.1). The treatment effect was estimated by calculating the mean difference (MD) with 95% confidence intervals (CIs). Seven trials involving 258 participants met the inclusion criteria. In this sample size, H-CS lighting was associated with a significant reduction in depressive symptoms (MD = −5.56, 95% CI = −9.22 to −1.90, P = 0.003, I2 = 64%). According to the meta-analysis, CS can be employed for the clinical evaluation of BLT for patients with depressive disorder and exposure to H-CS lighting significantly reduced depressive symptoms among adults. A range of CS > 0.57 was obtained, during which different lighting parameter combinations (e.g., light levels, spectra, duration, and light distribution) could achieve better treatment for depression.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253648.
Glymphatic system in the thalamus, secondary degeneration area was severely impaired at 2nd week after transient occlusion of the middle cerebral artery in rats
Authors: Li Chanchan , Lin Luyi , Sun Chengfeng , Hao Xiaozhu , Yin Lekang , Zhang Xiaoxue , Tian Jiaqi , Yao Zhengwei , Feng Xiaoyuan , Yang Yanmei
Published: October 2022

Background and objectives

The glymphatic system is a recently discovered cerebrospinal fluid transport system and little is known about its dynamic changes after stroke. This study aimed to dynamically observe the structural and functional changes of the impaired glymphatic system in the thalamus after ischemic stroke by pathology and MRI.

Materials and methods

Ischemic stroke was induced by the middle cerebral artery occlusion (MCAO) model. A total of 20 Sprague-Dawley rats were randomly assigned into four groups: sham, MCAO 1 week, MCAO 2 week, and MCAO 2 month. All rats successively underwent neurological examination, dynamic contrast-enhanced MRI (DCE-MRI), and immunofluorescence staining. Immunofluorescence staining of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), ionized calcium-binding adaptor molecule 1 (Iba1), and beta-amyloid precursor protein (APP) were done in thalamus ventroposterior nucleus.

Results

The astrocyte and microglial activation and the APP deposition in the MCAO 2 week group were the highest (P < 0.05 for all). The AQP4 polarization rates of the MCAO 2 week and 2 month groups were the lowest (P < 0.05 for all). Although there was no correlation between histological changes and MRI metrics in all four groups (P > 0.05 for all), the tendency of the APP deposition was nearly consistent with the one of the contrast agent retention in DCE-MRI.

Conclusion

The glymphatic system in the thalamus was severely impaired at 2nd week after MCAO, and may be revealed by DCE-MRI. This study may provide a relevant theoretical basis for making a thorough inquiry of the mechanism of brain injury after stroke and clinical treatment of ischemic stroke and help readers appreciate the importance of DCE-MRI.
Diagnostic management of patients reporting symptoms after wheat ingestion
Authors: Costantino Andrea , Aversano Gloria Maria , Lasagni Giovanni , Smania Veronica , Doneda Luisa , Vecchi Maurizio , Roncoroni Leda , Pastorello Elide Anna , Elli Luca
Published: October 2022

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.
Ozone treatment promotes physicochemical properties and antioxidant capacity of fresh-cut red pitaya based on phenolic metabolism
Authors: Li Chen , Wang Shan , Wang Jiayi , Wu Zhaohui , Xu Yaping , Wu Zhaoxia
Published: October 2022

Pitaya is an important fresh-cut product in the global fruit market. The health benefits of fresh-cut red pitaya fruit are attributed to its unique phenolic content and other antioxidants, but the fruit is highly susceptible to spoilage which causes a decline in nutritional quality. In this study, we monitored changes in quality and phenolic compounds of pitaya fruit treated with gaseous ozone during storage at 8 ± 2°C for 4 days. Compared with the control group, ozone treatment was an effective strategy for preserving quality by controlling the growth of microorganisms, preventing weight loss and softening, and improving the content of soluble solids and titratable acids. The results showed that ozone induced the accumulation of phenolic compounds while maintaining the quality. The content of phenolic compounds in fresh-cut pitaya was positively correlated with antioxidant activity. Ultra-performance liquid chromatography-electrospray tandem mass spectrometry was used to fingerprint the phenolic metabolites and metabolomic analysis identified 26 phenolic compounds. The majority of these were phenylpropanoids, and the key metabolic pathways were phenylpropane metabolism and flavonoid synthesis. This study illustrated the mechanism by which of ozone prolongs the shelf life of fresh-cut pitaya fruit and validated ozone as a valuable phenolic inducer and regulator of antioxidant activity, positively influencing the potential health benefits of fresh-cut products.
Nutritional status and function after high-calorie formula vs. Chinese food intervention in undernourished children with cerebral palsy
Authors: Zhao Yiting , He Lu , Peng Tingting , Liu Liru , Zhou Hongyu , Xu Yunxian , Yang Xubo , Huang Yuan , Chen Zhaofang , Xu Yi , Li Jinling , Hou Xiaohui , Tang Hongmei , Xu Kaishou
Published: October 2022

Aim

To investigate the efficacy and safety of high-calorie formula vs. Chinese daily food on the nutritional status and motor function of undernourished children with cerebral palsy (CP).

Methods

In this prospective, assessor-blind, and randomized controlled trial, we recruited children (1–10 years) with CP and undernutrition based on the WHO and the American Society for Parenteral and Enteral Nutrition criteria from the National Children's Medical Center. Participants were randomly allocated (1:1) to a high-calorie formula group or a Chinese daily food diet group (control group) for 6 months. Indirect calorimetry was used to estimate energy requirements. We compared the nutritional status and gross motor function of participants in both groups based on weight, height, z-scores (weight-for-age, height-for-age, weight-for-height, and BMI-for-age), and the Gross Motor Function Measure (GMFM), respectively, at baseline, 3-, and 6-months follow-up. In addition, the effective rate of nutritional intervention, and adverse events were simultaneously assessed.

Results

From July 2020 to December 2021, a total of 119 participants were enrolled and randomized, and 110 participants completed the study (with 54 children in the high-calorie formula group and 56 children in the control group). After 6 months of treatment, the weight, height, z-scores (weight-for-height, weight-for-age, and BMI-for-age), and GMFM of both groups were significantly improved (p < 0.05). There were significant differences in changes in weight, weight-for-age z-scores, and GMFM between the two groups (p < 0.05). During the study period, 16 children experienced at least one mild adverse event [9 (16.7%) in the formula group and 7 (12.5%) in the control group].

Conclusion

Nutritional intervention with a high-calorie formula may be an effective and safe option in children with CP for improving undernutrition and gross motor dysfunction.

Clinical trial registration

www.chictr.org.cn, identifier: ChiCTR2000033878.
Association between dietary inflammatory index and metabolic syndrome: Analysis of the NHANES 2005–2016
Authors: Zhang Xiaochen , Guo Yinpei , Yao Nan , Wang Ling , Sun Mengzi , Xu Xiaomeng , Yang Huanshuai , Sun Yang , Li Bo
Published: October 2022

Objective

Metabolic syndrome (MetS) is a global problem that increasingly violates human health and quality of life. We explored the relationship between dietary inflammatory potential represented by dietary inflammatory index (DII) and the occurrence of MetS to provid data support for the prevention of it through dietary structure intervention.

Methods

The data was come from National Health and Nutrition Examination Survey 2007–2018, including demographic, dietary, questionnaire variables and laboratory indicators. MetS was defined according to the criteria proposed by the American Endocrine Association (ACE) and the American Society of Clinical Endocrinology (ACCE). DII was calculated using the scoring method established by Shivappa. We divided DII scores into 4 quartiles, the chi-square test was used to compare the variable difference between DII quartiles groups. A logistic regression model was used to analyze the association between DII and MetS. We also performed subgroup analysis. A generalized linear regression model was used to explore the association of DII level and the levels of seven MetS related biochemical indicators.

Results

The final sample size was 8,180, and the DII scores of the subjects were −5.50 to 5.22. The proportions of men, young people, non-Hispanic blacks, poor people, smokers, and MetS patients in the Q1–Q4 DII quantiles groups were gradually increased. The risk of MetS in the Q4 group which had highest dietary inflammatory degree was 1.592 (1.248, 2.030) times higher than that in the Q1 group, respectively (P < 0.001). After subgroup analysis, women, youth, non-smokers and alcohol drinkers were found to be more sensitive to the dietary inflammation. Then we found that the level of DII was significantly positively correlated with waist circumference (WC), body mass index (BMI), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but negatively correlated with high density lipoprotein cholesterol (HDL-C).

Conclusions

In the research subjects, the degree of dietary inflammation was associated with the occurrence of MetS and significantly affected WC, BMI, blood pressure, and blood lipid levels. It is necessary to conduct investigations and early dietary interventions for women and young people to prevent the occurrence of chronic metabolic diseases.
Case report: Immune-mediated meibomian gland dysfunction following pembrolizumab therapy for advanced urothelial carcinoma
Authors: Nguyen Charles B. , Su Christopher T. , Morgan Meredith , Alva Ajjai S.
Published: October 2022

Ocular immune-related adverse events are a relatively rare complication of immune checkpoint inhibitors. Common ocular toxicities range from dry eyes to inflammatory uveitis and ocular myasthenia gravis. Here, we present the case of a 55-year-old woman with recurrent urothelial carcinoma of the ureter after initially being managed with neoadjuvant cisplatin-based chemotherapy and surgical resection. She was treated with pembrolizumab which was complicated by immune-mediated pneumonitis after the eighth cycle, which was managed with a prolonged steroid course. The patient also developed red eyes along with recurrent styes. Eye examination revealed decreased tear breakup time, expression of thick and turbid meibum, and meibomian gland atrophy on infrared meibography. The patient was diagnosed with suspected immune-mediated meibomian gland dysfunction (MGD) as a result of pembrolizumab, a previously unreported complication of immunotherapy. The goal of MGD therapy is to stabilize the tear film and minimize evaporation with lipid-based lubricants and other conservative treatments.
Genetic risk, incident colorectal cancer, and the benefits of adhering to a healthy lifestyle: A prospective study using data from UK Biobank and FinnGen
Authors: Wu E. , Ni Jun-Tao , Chen Xin , Zhu Zhao-Hui , Xu Hong-Quan , Tao Lin , Xie Tian
Published: October 2022

Background

Genetic factors increase the individual risk of colorectal cancer (CRC); however, the extent to which a healthy lifestyle can offset increased genetic risk is unknown. This study investigated whether a healthy lifestyle is associated with lower CRC risk, regardless of genetic risk.

Methods

We recruited 390,365 participants without cancer at baseline (2006–2010) from the UK Biobank. The primary outcome was CRC incidence. A healthy lifestyle score constructed using 16 factors of six dimensions (smoking, drinking, body mass index, diet, exercise, and sleep) was categorized into three risk categories: favorable, intermediate, and unfavorable. To calculate the polygenic risk scores (PRSs) of UK Biobank participants, we extracted 454,678 single nucleotide polymorphisms (SNPs) from the UK Biobank and FinnGen Biobank after quality control. Cox proportional hazards regression was performed to evaluate the associations and was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

During a median follow-up of 10.90 years, 4,090 new CRC cases were reported in the UK Biobank. The “best-fit” PRSs were constructed using 59 SNPs based on the UK Biobank cohort and FinnGen genome-wide association study summary data (R2 = 0.23%) and were divided into low (lowest quintile), intermediate (including second–fourth quintile), and high (highest quintile) genetic risk categories. The multivariate-adjusted Cox model revealed that participants with favorable lifestyles had HRs of 0.66 (95% CI = 0.60–0.72) for developing CRC vs. those with unfavorable lifestyles; low genetic risk was associated with a decreased risk of CRC (HR = 0.67, 95% CI =0.61–0.74) compared with those with high genetic risk. The HRs for low genetic risk participants with favorable lifestyles were 0.44 (95% CI =0.36–0.55) vs. participants with high genetic risk and unfavorable lifestyles. Among the participants with low, intermediate, or high genetic risk, the HRs of favorable vs. unfavorable lifestyles were 0.74, 0.64, and 0.72 (all p< 0.05).

Conclusions

Low genetic risk and a favorable lifestyle were significantly associated with a decreased risk of CRC. A favorable lifestyle was associated with a lower CRC risk, regardless of genetic risk.
Construction and validation of a nomogram to predict overall survival in patients with breast sarcoma
Authors: Cheng Yixin , Zhang Pengkun , Huang Yulin , Tang Ru , Zhang Lei , Sun Jiayuan , Chi Feng , Wu San-Gang , He Zhenyu
Published: October 2022

Background

This study aimed to construct a nomogram for Breast sarcoma (BS) to predict the prognosis of patients with BS accurately and provide a theoretical basis for individualized treatment.

Methods

Patients selected from the Surveillance, Epidemiology and End Results (SEER) database from 2000 to 2018 were assigned to a training group (TG, n = 696) and an internal validation group (IVG, n = 299) at a 7:3 ratio. Cox regression analysis was performed on the TG, and statistically significant factors were used to establish a nomogram to predict 3-, 5-, and 10-year overall survival (OS). The nomogram’s predictive power was validated using data from patients who attended our institution as the external validation group (EVG, n =79).

Results

Cox regression analysis identified five factors, which were used to construct the nomogram. Good prediction accuracy was demonstrated using calibration curves. The concordance (C) indices for TG = 0.804 (95% confidence interval (CI) 0.777–0.831) and IVG = 0.761 (0.716–0.806) were higher than those based on 8th American Joint Committee on Cancer (AJCC8) stage: TG = 0.695 (0.660–0.730), IVG = 0.637 (0.584–0.690). The EVG also had a high C-index: 0.844 (0.768–0.920). Decision curve analysis showed that nomogram has larger net benefits than the AJCC8. The Kaplan–Meier curves of the nomogram-based risk groups showed significant differences (p < 0.001).

Conclusions

The nomogram could accurately predict 3-, 5-, and 10-year OS and provided nomogram-based risk stratification, which could help physicians to personalize treatment plans for patients with BS.
Monoclonal antibodies in cervical malignancy-related HPV
Authors: Aghbash Parisa Shiri , Hemmat Nima , Fathi Hamidreza , Baghi Hossein Bannazadeh
Published: October 2022

Despite many efforts to treat HPV infection, cervical cancer survival is still poor for several reasons, including resistance to chemotherapy and relapse. Numerous treatments such as surgery, radiation therapy, immune cell-based therapies, siRNA combined with various drugs, and immunotherapy are being studied and performed to provide the best treatment. Depending on the stage and size of the tumor, methods such as radical hysterectomy, pelvic lymphadenectomy, or chemotherapy can be utilized to treat cervical cancer. While accepted, these treatments lead to interruptions in cellular pathways and immune system homeostasis. In addition to a low survival rate, cervical neoplasm incidence has been rising significantly. However, new strategies have been proposed to increase patient survival while reducing the toxicity of chemotherapy, including targeted therapy and monoclonal antibodies. In this article, we discuss the types and potential therapeutic roles of monoclonal antibodies in cervical cancer.
Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma - A Multi-Center, Randomized, Controlled Trial (pro-duct001)
Authors: Schmelzle Moritz , Benzing Christian , Fischer Lutz , Herden Uta , Sterneck Martina , Settmacher Utz , Bauschke Astrid , Neumann Ulf , Pelzer Uwe , Müller Tobias , Strassburg Christian , Lang Hauke , Becker Thomas , Königsrainer Alfred , Nadalin Silvio , Quante Markus , Paul Andreas , Friess Helmut , Klempnauer Jürgen , Richter Nicolas , Vondran Florian , Pascher Andreas , Rösch Thomas , Schöning Wenzel , Krenzien Felix , Öllinger Robert , Seehofer Daniel , Neuhaus Peter , Pratschke Johann
Published: October 2022

Background

Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT.

Methods

We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates.

Results

Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively.

Conclusions

This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.
Real world data on light chain cardiac amyloidosis: Still a delayed diagnosis
Authors: Chatzileontiadou Sofia , Zegkos Thomas , Frouzaki Christina , Apsemidou Athanasia , Efthimiadis Georgios , Parcharidou Despoina , Papaioannou Maria
Published: October 2022

Cardiac amyloidosis (CA) represents a myocardial disorder developed by fibril deposition of a heterogeneous group of misfolding proteins. Despite being rare, a high clinical index of suspicion and novel advanced diagnostic methods seem to facilitate its early recognition. Currently nine types of cardiac amyloidosis have been described with AL and ATTR being the most common. Light chain amyloidosis (AL) is a life-threatening disease, resulting from clonal plasma cells that produce amyloidogenic light chain fragments causing organ damage including the heart. Morbidity and mortality of these patients is strongly associated with the severity of cardiac involvement. Thus, early and precise diagnosis is crucial for prompt treatment initiation. In this study, we retrospectively analyzed data of 36 consecutive patients who were diagnosed with AL amyloidosis and treated in our center over the past 15 years. Heart involvement was present in 33 (92%) of them while 76% had severe cardiac disease as of stage IIIa and IIIb, according to the Mayo2004/European staging system. Almost one third of these patients experienced an early death occurring the first five months of diagnosis. To capture everyday clinical practice, we provide details on clinical presentation, diagnostic challenges, and outcome of these patients.
Ultrasound-guided posterior quadratus lumborum block can reduce postoperative opioid consumption and promote rapid recovery in patients undergoing sutureless laparoscopic partial nephrectomy: A triple-blind, randomized, controlled study
Authors: Zhu Youzhuang , Li Zhichao , Qin Shangyuan , Xu Hao , He Jianshuai , Sheng Fang , Zhao Qin , Kang Yihan , Gao Xin , Li Si , Chai Jun , Chen Lina , Wang Weiwei
Published: October 2022

Purpose

We hypothesized that posterior quadratus lumborum block would reduce postoperative opioid consumption and improve the quality of recovery in patients undergoing sutureless laparoscopic partial nephrectomy.

Materials and methods

The study included 60 patients, ages 18−65 with American Society of Anesthesiologists scores of I-II scheduled for elective sutureless laparoscopic partial nephrectomy. Before general anesthesia, 60 participating patients were randomly allocated to receive a 30-ml injection posterior to the quadratus lumborum muscle with either 0.375% ropivacaine (n = 30) or normal saline (n = 30). The primary outcomes included cumulative opioid consumption within 12 h postoperatively and quality of postoperative recovery at 48 h. Secondary outcomes included the Numerical Rating Scale (NRS), opioid consumption by period, first time to press the analgesic pump, number of patients needing rescue analgesia, blood glucose and cortisol concentrations, early postoperative recovery indicators, and adverse events.

Results

There were 48 patients included in the final analysis. The intervention group had lower cumulative consumption of sufentanil within 12 h postoperatively and higher quality of postoperative recovery scores at 48 h postoperatively compared with the control group (p < 0.001). The NRS at resting and movement of the intervention group was lower at 0 h, 6 h, and 12 h after surgery than in the control group (p < 0.05). At prespecified intervals (0 to 2 h, 2 to 6 h, 6 to 12 h, 12 to 24 h, and 24 to 48 h) after surgery, the intervention group had lower consumption of sufentanil compared with the control group (p < 0.05). The intervention group took longer to press the analgesic pump for the first time within 48 h after surgery compared with the control group (p < 0.001). The postoperative blood glucose and cortisol concentrations in the intervention group were lower than in the control group (p < 0.05). The times to first excretion, ambulation, and discharge were shorter in the intervention group compared with the control group (p < 0.05). There was no significant difference in adverse events between the two groups.

Conclusions

Our trial demonstrated that patients who received posterior quadratus lumborum block had significantly lower opioid consumption within 12 h postoperatively and had a better quality of recovery at 48 h postoperatively. Therefore, we recommend posterior quadratus lumborum block as an option for postoperative analgesia in patients undergoing sutureless laparoscopic partial nephrectomy.

Trial Registration

http://www.chictr.org.cn, identifier ChiCTR2100053439.