bluuebunny/crossref_metadata_2025 huggingface dataset:
Anesthesia and Oncology: Friend or Foe?
Authors: Buddeberg Bigna S. , Seeberger Manfred D.
Published: March 2022

Cancer is a leading cause of death, and surgery is an important treatment modality. Laboratory research and retrospective studies have raised the suspicion that the choice of anesthetics for cancer surgery might affect the course of cancerous disease. The aim of this review is to provide a critical overview of the current state of knowledge. Inhalational anesthesia with volatiles or total intravenous anesthesia (TIVA) with propofol are the two most commonly used anesthetic techniques. Most data comparing volatile anesthetics with TIVA is from either in vitro or retrospective studies. Although conflicting, data shows a trend towards favoring propofol. Opioids are commonly used in anesthesia. Data on potential effects of opioids on growth and recurrence of cancer are scarce and conflicting. Preclinical studies have shown that opioids stimulate cancer growth through the µ-opioid receptor. Opioids also act as immunosuppressants and, therefore, have the potential to facilitate metastatic spread. However, the finding of an adverse effect of opioids on tumor growth and cancer recurrence by some retrospective studies has not been confirmed by prospective studies. Regional anesthesia has not been found to have a beneficial effect on the outcome of surgically treated cancer patients, but prospective studies are scarce. Local anesthetics might have a beneficial effect, as observed in animal and in vitro studies. However, prospective clinical studies strongly question such an effect. Blood products, which may be needed during extensive cancer surgery suppress the immune system, and data strongly suggest a negative impact on cancer recurrence. The potential effects of other commonly used anesthetic agents on the outcome of cancer patients have not been sufficiently studied for drawing valid conclusions. In conclusion, laboratory data and most retrospective studies suggest a potential advantage of TIVA over inhalational anesthesia on the outcome of surgical cancer patients, but prospective, randomized studies are missing. Given the state of weak scientific evidence, TIVA may be used as the preferred type of anesthesia unless there is an individual contraindication against it. Studies on the effects of other drugs frequently used in anesthesia are limited in number and quality, and have found conflicting results.
Surgical Management of Brain Metastasis: Challenges and Nuances
Authors: Ene Chibawanye I. , Ferguson Sherise D.
Published: March 2022

Brain metastasis is the most common type of intracranial tumor. The contemporary management of brain metastasis is a challenging issue and traditionally has carried a poor prognosis as these lesions typically occur in the setting of advanced cancer. However, improvement in systemic therapy, advances in radiation techniques and multimodal therapy tailored to the individual patient, has given hope to this patient population. Surgical resection has a well-established role in the management of brain metastasis. Here we discuss the evolving role of surgery in the treatment of this diverse patient population.
Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions
Authors: Rodwin Rozalyn L. , Siddiq Namrah Z. , Ehrlich Barbara E. , Lustberg Maryam B.
Published: March 2022

Chemotherapy induced peripheral neuropathy (CIPN) is an often severe and debilitating complication of multiple chemotherapeutic agents that can affect patients of all ages, across cancer diagnoses. CIPN can persist post-therapy, and significantly impact the health and quality of life of cancer survivors. Identifying patients at risk for CIPN is challenging due to the lack of standardized objective measures to assess for CIPN. Furthermore, there are no approved preventative treatments for CIPN, and therapeutic options for CIPN remain limited once it develops. Biomarkers of CIPN have been studied but are not widely used in clinical practice. They can serve as an important clinical tool to identify individuals at risk for CIPN and to better understand the pathogenesis and avenues for treatment of CIPN. Here we review promising biomarkers of CIPN in humans and their clinical implications.
Serum Calprotectin Is a Valid Biomarker in Distinction of Bacterial Urinary Tract Infection From Viral Respiratory Illness in Children Under 3 Years of Age
Authors: Lamot Mirta , Miler Marijana , Nikolac Gabaj Nora , Lamot Lovro , Milošević Milan , Harjaček Miroslav , Abdović Slaven
Published: March 2022

Background

Febrile illnesses in young children can be a major diagnostic challenge, despite the routine use of various laboratory markers. Recent advancements in the understanding of inflammatory processes have highlighted the role of calprotectin, a heterodimer consisting of S100A8 and S100A9 proteins, with many studies suggesting its clinical value as a biomarker of inflammation. This research aimed to evaluate the usefulness of serum calprotectin (sCal) as a biomarker of urinary tract infection (UTI), which was due to its high pooled prevalence and feasibility of urine culture as a diagnostic reference standard selected for a model of bacterial infection in children.

Methods

Febrile children aged 0–36 months with suspected UTI based on positive urinalysis or viral respiratory tract infection were included. Children with significant bacteriuria in urine culture were labeled as cases (n = 58), while those with confirmed viral infection (n = 51), as well as those with suspected UTI but sterile urine culture who went on to develop symptoms consistent with viral respiratory infection (n = 7), were labeled as controls. sCal levels were determined by a commercial immunoassay. Conventional inflammation markers (C-reactive protein, procalcitonin, white blood cell count, absolute neutrophil count, and neutrophil percentage) were measured on the day of the clinical examination. Differences in measured inflammatory markers between cases and controls were analyzed with Mann-Whitney U-test. ROC analysis reported cut-off values with the best sensitivity and specificity to distinguish bacterial UTI from viral respiratory infection.

Results

All analyzed inflammatory biomarkers, including sCal, were significantly higher in cases than in controls. Median concentration of sCal was 4.97 μg/mL (IQR 3.43–6.42) and 2.45 μg/mL (IQR 1.63–3.85) for cases and controls, respectively (p < 0.001). For identifying bacterial UTI, sensitivity and specificity of sCal were 77.6 and 69.0%, respectively, at an adjusted cut-off point of >3.24 μg/mL (AUC 80.2%).

Conclusion

sCal could have substantial added value in the management of a child with fever and positive urinalysis and is a promising biomarker in distinction between bacterial UTI and viral respiratory causes of febrile illness in children under the age of 3 years.
Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure
Authors: Radhakrishnan Rupa , Vishnubhotla Ramana V. , Zhao Yi , Yan Jingwen , He Bing , Steinhardt Nicole , Haas David M. , Sokol Gregory M. , Sadhasivam Senthilkumar
Published: March 2022

Background

Infants with prenatal opioid and substance exposure are at higher risk of poor neurobehavioral outcomes in later childhood. Early brain imaging in infancy has the potential to identify early brain developmental alterations that may help predict behavioral outcomes in these children. In this study, using resting-state functional MRI in early infancy, we aim to identify differences in global brain network connectivity in infants with prenatal opioid and substance exposure compared to healthy control infants.

Methods and Materials

In this prospective study, we recruited 23 infants with prenatal opioid exposure and 29 healthy opioid naïve infants. All subjects underwent brain resting-state functional MRI before 3 months postmenstrual age. Covariate Assisted Principal (CAP) regression was performed to identify brain networks within which functional connectivity was associated with opioid exposure after adjusting for sex and gestational age. Associations of these significant networks with maternal comorbidities were also evaluated. Additionally, graph network metrics were assessed in these CAP networks.

Results

There were four CAP network components that were significantly different between the opioid exposed and healthy control infants. Two of these four networks were associated with maternal psychological factors. Intra-network graph metrics, namely average flow coefficient, clustering coefficient and transitivity were also significantly different in opioid exposed infants compared to healthy controls.

Conclusion

Prenatal opioid exposure is associated with alterations in global brain functional networks compared to non-opioid exposed infants, with intra-network alterations in graph network modeling. These network alterations were also associated with maternal comorbidity, especially mental health. Large-scale longitudinal studies can help in understanding the clinical implications of these early brain functional network alterations in infants with prenatal opioid exposure.
Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
Authors: Sheng Lei , Hu Fan , Yu Hanqing , Tao Xueyou , Jia Rumeng , Gu Yufeng , Chen Lu , Kong Hong , Miao Chen , Fei Wenjing , Yang Yang , Jia Jinhui , Zhu Xia , He Xueming , Hu Liang , Ma Jianxin , Liu Wen-Tao , Yang Mi
Published: March 2022

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “inflammation brake.” We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.
Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions
Authors: Meng Long , Huang Jing , Qiu Feng , Shan Xuefeng , Chen Lin , Sun Shusen , Wang Yuwei , Yang Junqing
Published: March 2022

Backgrounds: Proteasome inhibitors (PI) cause toxic peripheral neuropathy (PN), which is one of the dose-limiting adverse events of these treatments. Recent preclinical studies find that factor Xa inhibitor (FXaI), rivaroxaban, promotes PN in animals receiving oxaliplatin. Cancer patients can receive combined therapy of PI and FXaI. This study aimed to identify and characterize the interaction signals for the concomitant use of PI and FXaI resulting in PN.

Methods: Reports from the United States FDA Adverse Event Reporting System (FAERS) were extracted from the first quarter of 2004 to the first quarter of 2020 for analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) query was used to identify PN cases. We conducted an initial disproportionality investigation to detect PN adverse event signals associated with the combined use of PI and FXaI by estimating a reporting odds ratio (ROR) with a 95% confidence interval (CI). The adjusted RORs were then analyzed by logistic regression analysis (adjusting for age, gender, and reporting year), and additive/multiplicative models were performed to further confirm the findings. Additionally, subset data analysis was performed on the basis of a single drug of PI and FXaI.

Results: A total of 159,317 adverse event reports (including 2,822 PN reports) were included. The combined use of PI and FXaI was associated with a higher reporting of PN (RORadj = 7.890, 95%CI, 5.321–11.698). The result remained significant based on additive/multiplicative methods. The observed association was consistent in the analysis restricted to all specific PI agents (bortezomib and ixazomib) and FXaI (rivaroxaban), except apixaban.

Conclusion: Analysis of FAERS data identified reporting associations of PN in the combined use of PI and FXaI, suggesting the need for more robust preclinical and clinical studies to elucidate the relationship.
Mitochondrial Protein Akap1 Deletion Exacerbates Endoplasmic Reticulum Stress in Mice Exposed to Hyperoxia
Authors: Sidramagowda Patil Sahebgowda , Soundararajan Ramani , Fukumoto Jutaro , Breitzig Mason , Hernández-Cuervo Helena , Alleyn Matthew , Lin Muling , Narala Venkata Ramireddy , Lockey Richard , Kolliputi Narasaiah , Galam Lakshmi
Published: March 2022

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are treated with high concentrations of supplementary oxygen. However, prolonged exposure to high oxygen concentrations stimulates the production of reactive oxygen species (ROS), which damages the mitochondria and accumulates misfolded proteins in the endoplasmic reticulum (ER). The mitochondrial protein A-kinase anchoring protein 1 (Akap1) is critical for mitochondrial homeostasis. It is known that Akap1 deficiency results in heart damage, neuronal development impairment, and mitochondrial malfunction in preclinical studies. Our laboratory recently revealed that deleting Akap1 increases the severity of hyperoxia-induced ALI in mice. To assess the role of Akap1 deletion in ER stress in lung injury, wild-type and Akap1−/− mice were exposed to hyperoxia for 48 h. This study indicates that Akap1−/− mice exposed to hyperoxia undergo ER stress, which is associated with an increased expression of BiP, JNK phosphorylation, eIF2α phosphorylation, ER stress-induced cell death, and autophagy. This work demonstrates that deleting Akap1 results in increased ER stress in the lungs of mice and that hyperoxia exacerbates ER stress-related consequences.
Deferoxamine Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis and Activating the Nrf2 Pathway
Authors: Guo Zhou , Lin Jiamin , Sun Kai , Guo Jiayou , Yao Xudong , Wang Genchun , Hou Liangcai , Xu Jingting , Guo Jiachao , Guo Fengjing
Published: March 2022

Objective: Osteoarthritis (OA) is a common disease with a complex pathology including mechanical load, inflammation, and metabolic factors. Chondrocyte ferroptosis contributes to OA progression. Because iron deposition is a major pathological event in ferroptosis, deferoxamine (DFO), an effective iron chelator, has been used to inhibit ferroptosis in various degenerative disease models. Nevertheless, its OA treatment efficacy remains unknown. We aimed to determine whether DFO alleviates chondrocyte ferroptosis and its effect on OA and to explore its possible mechanism.

Methods: Interleukin-1β (IL-1β) was used to simulate inflammation, and chondrocyte ferroptosis was induced by erastin, a classic ferroptosis inducer. A surgical destabilized medial meniscus mouse model was also applied to simulate OA in vivo, and erastin was injected into the articular cavity to induce mouse knee chondrocyte ferroptosis. We determined the effects of DFO on ferroptosis and injury-related events: chondrocyte inflammation, extracellular matrix degradation, oxidative stress, and articular cartilage degradation.

Results: IL-1β increased the levels of ROS, lipid ROS, and the lipid peroxidation end product malondialdehyde (MDA) and altered ferroptosis-related protein expression in chondrocytes. Moreover, ferrostatin-1 (Fer-1), a classic ferroptosis inhibitor, rescued the IL-1β–induced decrease in collagen type II (collagen II) expression and increase in matrix metalloproteinase 13 (MMP13) expression. Erastin promoted MMP13 expression in chondrocytes but inhibited collagen II expression. DFO alleviated IL-1β– and erastin-induced cytotoxicity in chondrocytes, abrogated ROS and lipid ROS accumulation and the increase in MDA, improved OA-like changes in chondrocytes, and promoted nuclear factor E2–related factor 2 (Nrf2) antioxidant system activation. Finally, intra-articular injection of DFO enhanced collagen II expression in OA model mice, inhibited erastin-induced articular chondrocyte death, and delayed articular cartilage degradation and OA progression.

Conclusion: Our research confirms that ferroptosis occurs in chondrocytes under inflammatory conditions, and inhibition of chondrocyte ferroptosis can alleviate chondrocyte destruction. Erastin-induced chondrocyte ferroptosis can stimulate increased MMP13 expression and decreased collagen II expression in chondrocytes. DFO can suppress chondrocyte ferroptosis and promote activation of the Nrf2 antioxidant system, which is essential for protecting chondrocytes. In addition, ferroptosis inhibition by DFO injection into the articular cavity may be a new OA treatment.
Brief Maternal Separation Inoculates Against the Effects of Social Stress on Depression-Like Behavior and Cocaine Reward in Mice
Authors: Calpe-López C. , Martínez-Caballero M. A. , García-Pardo M. P. , Aguilar M. A.
Published: March 2022

Exposure to intermittent repeated social defeat (IRSD) increases the vulnerability of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. According to the “inoculation of stress” hypothesis, a brief period of maternal separation (MS) can provide protection against the negative effects of IRSD. The aim of the present study was to assess whether exposure to a brief episode of MS prevents the subsequent short-term effects of IRSD on depression- and anxiety-like behaviors and to explore its long-term effects on cocaine CPP in mice. Four groups of male C57BL/6 mice were employed; two groups were separated from their mother [6 h on postnatal day (PND) 9], while the other two groups were not (controls). On PND 47, 50, 53 and 56, mice that had experienced MS were exposed to social defeat in the cage of an aggressive resident mouse (MS + IRSD group) or were allowed to explore an empty cage (MS + EXPL group). The same procedure was performed with control mice that had not experienced MS (CONTROL + IRSD and CONTROL + EXPL groups). On PND57-58, all the mice performed the elevated plus maze and the hole-board, social interaction and splash tests. Three weeks after the last episode of defeat, all the mice underwent the CPP procedure with cocaine (1 mg/kg). Irrespective of whether or not MS had taken place, a reduction in open arms measures, dips, and social interaction was observed in mice that experienced IRSD. A higher latency of grooming and acquisition of cocaine-induced CPP were observed only in mice exposed to IRSD alone (CONTROL + IRSD). These results suggest that exposure to a brief episode of stress early in life increases the subsequent resilience of animals to the effects of social stress on vulnerability to cocaine.
Discovery of Novel HPK1 Inhibitors Through Structure-Based Virtual Screening
Authors: Ge Huizhen , Peng Lizeng , Sun Zhou , Liu Huanxiang , Shen Yulin , Yao Xiaojun
Published: March 2022

Hematopoietic progenitor kinase (HPK1) is a negative regulator of T-cell receptor and B-cell signaling, which has been recognized as a novel antitumor target for immunotherapy. In this work, Glide docking-based virtual screening and kinase inhibition assay were performed to identify novel HPK1 inhibitors. The kinase inhibition assay results demonstrated five compounds with IC50 values below 20 μM, and the most potent one (compound M074-2865) had an IC50 value of 2.93 ± 0.09 μM. Molecular dynamics (MD) simulations were performed to delve into the interaction of sunitinib and the identified compound M074-2865 with the kinase domain of HPK1. The five compounds identified in this work could be considered promising hit compounds for further development of HPK1 inhibitors for immunotherapy.
Continuous Activation of Dopamine Receptors Alleviates LPS-Induced Liver Injury in Mice via β-arrestin2 Dependent Akt/NF-κB Pathway
Authors: Li Mingan , Zhang Ce , Zhou Lin , Sun Xiaohui , Wang Tian , Fu Fenghua
Published: March 2022

Many studies showed that dopamine receptors (DRs) agonists have anti-inflammatory effects. Rotigotine, a non-ergot dopamine receptor agonist, mainly actives DRD2/DRD3/DRD1. Rotigotine extended-release microspheres (RoMS) are a sustained-release formulation that can release sustainably rotigotine for more than 7 days after a single dose of RoMS. This study aimed to investigate whether RoMS can attenuate the lipopolysaccharide (LPS)-induced liver injury of mice. The liver injury was evaluated by assaying serum transaminase and observing histopathological changes. The levels of pro-inflammatory cytokines in serum were also detected. Western blot was employed to assay the expression of proteins in the Akt/NF-κB pathway. The results showed that pre-administration with a single dose of RoMS could inhibit the increase of serum transaminase induced by LPS, alleviate the pathological damage of liver tissue, and decrease the levels of tumor necrosis factor-α and interleukin-6. In addition, RoMS decreased Toll-like receptor 4 protein expression in liver tissue. RoMS mitigated liver injury by activating DRs and negatively regulating the β-arrestin2-dependent Akt/NF-κB signaling pathway. The effects of RoMS could be weakened or abolished by the specific DRD2 antagonist, R121. In conclusion, activation of DRs inhibited the releases of pro-inflammatory cytokines and alleviated the immune-mediated liver injury induced by LPS in mice. The anti-inflammatory mechanism of RoMS may be related to the regulation of the β-arrestin2-dependent Akt/NF-κB signaling pathway.
Influence of Jamaican Cultural and Religious Beliefs on Adherence to Pharmacotherapy for Non-Communicable Diseases: A Pharmacovigilance Perspective
Authors: Brown Robyn , Bateman Caryl James , Gossell-Williams Maxine
Published: March 2022

Worldwide, socio-cultural determinants have been shown to influence the beliefs of patients about their health and decision making for treatment. This is consistent with the evidence that cultural and religious beliefs affect illness conceptualization and behaviors of Jamaican patients living with non-communicable diseases, such as diabetes mellitus and hypertension. Despite these known socio-cultural influences, an acknowledgment of relevance of adherence to pharmacotherapy has been grossly understudied. Furthermore, while poor adherence to pharmacotherapy, especially in the management of patients living with non-communicable diseases is associated with adverse drug reactions; reporting of such information in the pharmacovigilance process is inadequate. We review previous studies on the cultural and religious beliefs within the Jamaican context that may contribute to poor adherence to pharmacotherapy, especially among those patients living with non-communicable diseases. We support the ongoing perspective that current pharmacovigilance processes need retooling with the inclusion of socio-cultural influences on adherence to pharmacotherapy.
The Role of Different Afferent Systems in the Modulation of the Otolith-Ocular Reflex After Long-Term Space Flights
Authors: Glukhikh Dmitrii O. , Naumov Ivan A. , Schoenmaekers Catho , Kornilova Ludmila N. , Wuyts Floris L.
Published: March 2022

Background

The vestibular (otolith) function is highly suppressed during space flight (SF) and the study of these changes is very important for the safety of the space crew during SF missions. The vestibular function (particularly, otolith-ocular reflex–OOcR) in clinical and space medicine is studied using different methodologies. However, different methods and methodologies can influence the outcome results.

Objective

The current study addresses the question of whether the OOcR results obtained by different methods are different, and what the role is of the different afferent systems in the modulation of the OOcR.

Methods

A total of 25 Russian cosmonauts voluntarily took part in our study. They are crewmembers of long duration space missions on the International Space Station (ISS). Cosmonauts were examined in pre- and post-flight “Sensory Adaptation” and “Gaze Spin” experiments, twice before (preflight) and three times after SF (post-flight). We used two different video oculography (VOG) systems for the recording of the OOcR obtained in each experiment.

Results

Comparison of the two VOG systems didn’t result into significant and systematic differences in the OOcR measurements. Analysis of the static torsion otolith–ocular reflex (OOR), static torsion otolith–cervical–ocular reflex (OCOR) and static torsion otolith–ocular reflex during eccentric centrifugation (OOREC) shows that the OOREC results in a lower OOcR response compared to the OOR and OCOR (before flight and late post-flight). However, all OOcRs were significantly decreased in all cosmonauts early post-flight.

Conclusion

Analysis of the results of ocular counter rolling (OCR) obtained by different methods (OOR, OCOR, and OOREC) showed that different afferent systems (tactile-proprioception, neck-cervical, visual and vestibular afferent input) have an impact on the OOcR.
Modulation of Plasma Proteomic Profile by Regular Training in Male and Female Basketball Players: A Preliminary Study
Authors: Militello Rosamaria , Pinto Gabriella , Illiano Anna , Luti Simone , Magherini Francesca , Amoresano Angela , Modesti Pietro Amedeo , Modesti Alessandra
Published: March 2022

Monitoring fatigue and recovery during training periods contributes to identifying the best training methods to achieve sports performance. To date, little is known about sex-related differences in sports adaptations. The aim of the present study is to identify sex-related sports adaptation proteins in female basketball players and male basketball players using proteomics approach on plasma samples withdrawn from athletes during in-season training period but far from a competition. A cohort of 20 professional basketball players, 10 female (BF) and 10 male (BM), and 20 sedentary male (10 CM) and female (10 CF) as control, of comparable age and BMI, were involved in this study. Protein profiles of plasma samples obtained from BM, BF, CM, and CF were analyzed by two-dimensional electrophoresis (2-DE). Differentially expressed proteins were identified by mass spectrometry. The computational 2-DE gel image analysis pointed out 33 differentially expressed protein spots (ANOVA p-value < 0.05) and differences between male and female basketball players are more evident among the players than controls. The expression profile of 54.5% of the total proteins is affected by sports activity. Furthermore, 14 proteins are differentially expressed in basket female players in comparison with their relative controls while seven are differentially expressed in basket male players in comparison with their controls. In conclusion, we identify in female athletes a reduction in proteins related to transcription regulation, most of these modulate chronic inflammation confirming the anti-inflammatory effect of regular training in female muscle metabolism. In male and female athletes, we found a decrease in Transthyretin involved in muscle homeostasis and regeneration and Dermcidin a stress-induced myokine linked to inflammatory and it will be interesting to fully understand the role of its different isoforms in male and female skeletal muscle contraction.
Delayed Cutaneous Microvascular Responses With Non-consecutive 3 Days of Remote Ischemic Preconditioning
Authors: Kim Jahyun , Franke Warren D. , Lang James A.
Published: March 2022

The optimal frequency and duration of remote ischemic preconditioning (RIPC) that augments microvascular function is unknown. A single bout of RIPC increases cutaneous endothelial function for ∼48 h, whereas 1 week of daily RIPC bouts improves more sustained endothelium-independent function. We hypothesized that 3 days of RIPC separated by rest days (3QOD RIPC) would result in sustained increases in both endothelium-dependent and endothelium-independent functions. Cutaneous microvascular function was assessed in 13 healthy young participants (aged 20.5 ± 3.9 years; 5 males, 8 females) before 3QOD and then 24, 48, and 72 h and a week after 3QOD. RIPC consisted of four repetitions of 5 min of blood flow occlusion separated by 5 min of reperfusion. Skin blood flow responses to local heating (Tloc = 42°C), acetylcholine (Ach), and sodium nitroprusside (SNP) were measured using laser speckle contrast imaging and expressed as cutaneous vascular conductance (CVC = PU⋅mmHg–1). Local heating-mediated vasodilation was increased 72 h after 3QOD and the increased responsivity persisted a week later (1.08 ± 0.24 vs. 1.34 ± 0.46, 1.21 ± 0.36 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. 72 h, a week after 3QOD; P = 0.054). Ach-induced cutaneous vasodilation increased a week after 3QOD (0.73 ± 0.41 vs. 0.95 ± 0.49 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. a week after 3QOD; P < 0.05). SNP-induced cutaneous vasodilation increased 24 h after 3QOD (0.47 ± 0.28 vs. 0.63 ± 0.35 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. 24 h; P < 0.05), but this change did not persist thereafter. Thus, 3QOD induced sustained improvement in endothelium-dependent vasodilation but was not sufficient to sustain increases in endothelium-independent vasodilation.
Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling
Authors: Qin Xinghua , Liu Binghua , Gao Feng , Hu Yuanyuan , Chen Ziwei , Xu Jie , Zhang Xing
Published: March 2022

Gluconolactone (D-glucono-1,5-lactone or GDL) is a food additive which presents in dietary products such as tofu, yogurt, cheese, bread, wine, etc. GDL has long been considered as a free radical scavenger; however, its role in cardioprotection remains elusive. In this study, using a mouse model of myocardial ischemia/reperfusion (I/R) injury and a model of hypoxia/reoxygenation (H/R) in neonatal rat cardiomyocytes (NRCM), we explored the role of GDL in I/R injury. We found that GDL (5 mg/kg, i.p.) attenuated myocardial I/R injury as evidenced by decreased infarct size, release of cardiac injury markers and apoptosis. Additionally, GDL decreased reperfusion-induced arrhythmias and oxidative stress. These effects were also observed in parallel in vitro studies. Mechanistically, we found that GDL treatment was strongly associated with activation of pro-survival extracellular signal-regulated kinase (ERK) signaling both in vivo and in vitro, and pharmacological inhibition of ERK signaling via U0126 attenuated GDL-induced cardioprotection against H/R injury in NRCM cells. To reveal how GDL regulates ERK signaling, we predicted the putative targets of GDL by Swiss Target Prediction, and protein kinase C (PKC) emerged as the most promising target for GDL. By pharmacological intervention and immunofluorescence, we found that PKCε, an important member of the PKC family, was activated after GDL treatment in heart, thereby leading to ERK activation and cardioprotection against I/R injury. Taken together, our results demonstrated that GDL acts as a potent activator of PKCε and, thus, provides cardioprotection against I/R injury via activation of ERK signaling.
Integration of Transcriptome and Metabolome Provides New Insights to Flavonoids Biosynthesis in Dendrobium huoshanense
Authors: Yuan Yingdan , Zuo Jiajia , Zhang Hanyue , Li Runze , Yu Maoyun , Liu Sian
Published: March 2022

Dendrobium huoshanense is both a traditional herbal medicine and a plant of high ornamental and medicinal value. We used transcriptomics and metabolomics to investigate the effects of growth year on the secondary metabolites of D. huoshanense stems obtained from four different years of cultivation. In this study, a total of 428 differentially accumulated metabolites (DAMs) and 1802 differentially expressed genes (DEGs) were identified. The KEGG enrichment analysis of DEGs and DAMs revealed significant differences in “Flavonoid biosynthesis”, “Phenylpropanoid biosynthesis” and “Flavone and flavonol biosynthesis”. We summarize the biosynthesis pathway of flavonoids in D. huoshanense, providing new insights into the biosynthesis and regulation mechanisms of flavonoids in D. huoshanense. Additionally, we identified two candidate genes, FLS (LOC110107557) and F3’H (LOC110095936), which are highly involved in flavonoid biosynthesis pathway, by WGCNA analysis. The aim of this study is to investigate the effects of growth year on secondarily metabolites in the plant and provide a theoretical basis for determining a reasonable harvesting period for D. huoshanense.
SNAREs Regulate Vesicle Trafficking During Root Growth and Development
Authors: Luo Changxin , Shi Yumei , Xiang Yun
Published: March 2022

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins assemble to drive the final membrane fusion step of membrane trafficking. Thus, SNAREs are essential for membrane fusion and vesicular trafficking, which are fundamental mechanisms for maintaining cellular homeostasis. In plants, SNAREs have been demonstrated to be located in different subcellular compartments and involved in a variety of fundamental processes, such as cytokinesis, cytoskeleton organization, symbiosis, and biotic and abiotic stress responses. In addition, SNAREs can also contribute to the normal growth and development of Arabidopsis. Here, we review recent progress in understanding the biological functions and signaling network of SNAREs in vesicle trafficking and the regulation of root growth and development in Arabidopsis.
Options for Engineering Apomixis in Plants
Authors: Yin Pei Pei , Tang Li Ping , Zhang Xian Sheng , Su Ying Hua
Published: March 2022

In plants, embryogenesis and reproduction are not strictly dependent on fertilization. Several species can produce embryos in seeds asexually, a process known as apomixis. Apomixis is defined as clonal asexual reproduction through seeds, whereby the progeny is identical to the maternal genotype, and provides valuable opportunities for developing superior cultivars, as its induction in agricultural crops can facilitate the development and maintenance of elite hybrid genotypes. In this review, we summarize the current understanding of apomixis and highlight the successful introduction of apomixis methods into sexual crops. In addition, we discuss several genes whose overexpression can induce somatic embryogenesis as candidate genes to induce parthenogenesis, a unique reproductive method of gametophytic apomixis. We also summarize three schemes to achieve engineered apomixis, which will offer more opportunities for the realization of apomictic reproduction.
A Civil Body Politick: Governance, Community, and Accountability in Early New England
Authors: Aleksandrov Gleb V.
Published: March 2022

In the early XVII century, when the New England colonies were established, the English Crown, preoccupied with domestic matters, interfered little with matters of colonial administration. The government system created by the colonists, was inspired to a certain degree by the religious ideas shared by many Puritan colonists but was shaped by political necessity and social conditions specific to the colonies. This created a system characterized by a much higher degree of accountability than in England, ensured by numerous checks on government power, both formal and informal. The same principles, initially applied to governance in individual settlements were later used for the colonies and the Confederation of New England, the first major inter-colonial political union. Early New England serves as an example of practical application of ideas in many ways similar to (and in many ways drastically different from) what we today call democracy as a foundation of ultimately successful government. By modern standards, the representative nature of the New England government was very limited, since it excluded women, Native Americans and other marginalized groups from the political process. It was also deeply rooted in a specific set of religious ideas. Nevertheless, the principles of elected representative government, present in some form in many Western polities, rarely served as a foundation of those political systems, still in most cases monarchies with limited government accountability. In New England these principles formed the core of the government system. This essay explores the formation of the early New England political system, its underlying ideas, both religious and secular, the way it faced some of the challenges encountered in the first decades of English settlement in the New World, and its eventual dissolution under external pressure.
Depression and Reasoning Ability in Adolescents: Examining the Moderating Role of Growth Mindset
Authors: Hu Chen , Wang Cuicui , Liu Weiwei , Wang Daoyang
Published: March 2022

The present two-year longitudinal study aimed to examine the relationship between depression and reasoning ability in adolescents, and further investigated the modulation effect of growth mindset on this relationship. A total of 1,961 and 1,667 Chinese adolescents participated in the study for the first year (T1) and second year (T2), respectively. The results showed that T1 depression was negatively correlated with T1 growth mindset (r = −0.35, p < 0.001), T1 reasoning (r = −0.30, p < 0.001), and T2 reasoning (r = −0.23, p < 0.001). Regression analysis revealed that T1 depression and the interaction between T1 depression and T1 growth mindset significantly predicted T1 reasoning (β = −0.220/−0.044, all ps < 0.05). After controlling for gender, age, family socioeconomic status, and T1 reasoning ability, both T1 depression and the interaction between T1 depression and T1 growth mindset still significantly predicted T2 reasoning (β = −0.104/β = 0.054, all ps < 0.05). The simple slope analysis found that the negative correlation between depression and reasoning in the high growth mindset group was weaker than that of the low growth mindset group in both T1 and T2, suggesting that growth mindset plays a significant moderating role in the relationship between depression and reasoning. In conclusion, depression was negatively correlated with reasoning ability in adolescents, in addition, growth mindset moderated the relationship between depression and reasoning.
Examining the Prevalence and Risk Factors of School Bullying Perpetration Among Chinese Children and Adolescents
Authors: Xue Jia , Hu Ran , Chai Lei , Han Ziqiang , Sun Ivan Y.
Published: March 2022

Background and Objectives

School bullying threatens the health of children and adolescents, such as mental health disorders, social deviant behaviors, suicidal behaviors, and coping difficulties. The present study aims to address (1) prevalence rates of both traditional and cyber school bullying perpetration, and (2) the associations between self-control, parental involvement, experiencing conflicts with parents, experiencing interparental conflict, and risk behaviors, and school bullying perpetration among Chinese children and adolescents.

Method

This study used data from a national representative school bullying survey (n= 3,675) among children and adolescents from all grades (primary school 4th grade to high school 12th grade) in seven cities in China. Negative binomial regression was used to estimate the effects of these predictive factors on traditional and cyber school bullying perpetration, respectively. Seven control variables were included, such as gender, boarding school, family socioeconomic status, and parents’ education levels.

Results

The sample comprised 52% female, 18% at boarding school, 70% of the participants’ academic performance was average or above. Approximately 17.3% of the participants reported participating in traditional school bullying against their peers, and 7.8% perpetrated cyberbullying behaviors. Also, after controlling sociodemographic characteristics and high self-control, parental involvement reduced the likelihood of traditional and cyberbullying perpetrating. Experiencing interparental conflict and risk behavior was significantly associated with increased perpetration of traditional and cyber school bullying. We found that having a conflict with parents was significantly associated with cyberbullying perpetration.

Implications

Findings have implications for practice. Anti-bullying intervention programs targeting this population should consider these factors. For example, school administrators may develop school programs involving parents in the efforts and interventions workshops improving children and adolescents’ levels of self-control. Limitations are also discussed.
Changes in Cognitive Outcomes in Early Childhood: The Role of Family Income and Volatility
Authors: Sosu Edward M. , Schmidt Peter
Published: March 2022

Associations between family income and child developmental outcomes are well documented. However, family income is not static but changes over time. Although this volatility represents income shocks that are likely to affect children’s lives, very few studies have so far examined its effect on early cognitive development. This study investigated associations between family income, volatility, and changes in cognitive outcomes in early childhood and examined whether these associations are dependent on a family’s overall income position. Data for the study spanned five waves of the Growing Up in Scotland longitudinal survey (N = 3,621). Findings indicate that income volatility was more prevalent among disadvantaged sociodemographic groups. In addition to average income, short-term volatility was associated with changes in child cognitive outcomes from ages 3 to 5. While upward volatility was associated with gains in expressive vocabulary, downward and fluctuating volatility were associated with declines in child problem-solving abilities. The association between volatility and changes in cognitive outcomes was similar for both children living in poverty and those from medium–high-income households. Our results suggest that policies aiming to cushion all families from negative income shocks, boost family income to ensure stability, and take low-income families out of poverty will have a significant impact on children’s cognitive development. Additionally, a more nuanced conceptualization of income is needed to understand its multidimensional impact on developmental outcomes.
The Multinational New Ventures on Corporate Performance Under the Work Environment and Innovation Behavior
Authors: Wang Zheng , Zong Ke , Jin Kim Hyun
Published: March 2022

To cope with economic globalization and improve the competitiveness of transnational start-ups, the impact of the work environment and innovation behavior on corporate performance of multinational new ventures is analyzed. First, a model of the interaction among environment, innovation behavior, and enterprise performance is proposed. Then, 296 transnational start-ups in coastal areas are surveyed, and the model results are analyzed. Finally, a series of results are obtained. The results show that from the perspective of psychology, work dynamic organizational learning environment has a positive impact on enterprise performance (standardized path coefficient 0.436, p < 0.01), and resource environment has a significant positive impact on enterprise performance (standardized path coefficient 0.425, p < 0.01). Strategic environment also positively affects enterprise performance (standardized path coefficient 0.474, p < 0.01). Therefore, the working environment of multinational new ventures has a positive impact on firm performance, and the mediating function between the working environment and firm performance is firm innovation behavior. With the research to achieve enterprise innovation of multinational new ventures by improving their response to the dynamic environment, the corporate performance has been greatly promoted, and finally, the new ventures would participate in the international market competition.
Restoring Connectedness in and to Nature: Three Nordic Examples of Recontextualizing Family Therapy to the Outdoors
Authors: Mattsson Markus , Fernee Carina Ribe , Pärnänen Kanerva , Lyytinen Pekka
Published: March 2022

Mentalization-based family therapy and family rehabilitation represent a rich variety of approaches for assisting families with difficult interaction patterns. On the other hand, adventure therapy methods have been successfully used with families to offer them empowering experiences of succeeding together against difficult odds and to improve communication between family members. Further, the health promoting qualities of spending time outdoors are now well established and recognized. The Nordic approach to mentalization-based family rehabilitation combines adventure, outdoor, and systemic therapy. We provide three examples of nature-based family rehabilitation practices that are delivered as brief, multi-family psychological interventions taking place in nearby nature and aiming to support sustainable, systemic change. The current contribution is a description of clinical practice, not a systematic review or a formal evaluation. We propose that recontextualizing mentalization-based family rehabilitation to the outdoors can not only provide added health benefits, but also strengthen intra-familial attuned interaction and emotional connectedness. The outdoor adventure provides the families with embodied, multisensory experiences of verbal and, especially, non-verbal interaction that can be usefully examined through the lens of theory of mentalization. The concreteness of adventure experiences is particularly beneficial for families that have difficulties in verbal communication and/or utilizing executive functions, perhaps due to neuropsychiatric traits, intellectual disabilities, or learning difficulties. Furthermore, outdoor adventure can support the participants’ connectedness to nature.
Associations Between Frailty and Inflammation, Physical, and Psycho-Social Health in Older Adults: A Systematic Review
Authors: Pothier Kristell , Gana Wassim , Bailly Nathalie , Fougère Bertrand
Published: March 2022

Frailty is a complex geriatric syndrome with multifactorial associated mechanisms that need to be examined more deeply to help reverse the adverse health-related outcomes. Specific inflammatory and physical health markers have been associated with the onset of frailty, but the associations between these factors and psycho-social health outcomes seem less studied. This systematic review aimed to identify, in the same study design, the potential associations between frailty and markers of inflammation, and physical or psycho-social health. A literature search was performed from inception until March 2021 using Medline, Psycinfo, and EMBASE. Three raters evaluated the articles and selected 22 studies, using inclusion and exclusion criteria (n = 17,373; 91.6% from community-dwelling samples). Regarding biomarkers, 95% of the included studies showed significant links between inflammation [especially the higher levels of C-reactive protein (CRP) and interleukin-6 (IL-6)], and frailty status. Approximately 86% of the included studies showed strong links between physical health decline (such as lower levels of hemoglobin, presence of comorbidities, or lower physical performance), and frailty status. At most, 13 studies among the 22 included ones evaluated psycho-social variables and mixed results were observed regarding the relationships with frailty. Results are discussed in terms of questioning the medical perception of global health, centering mostly on the physical dimension. Therefore, the development of future research studies involving a more exhaustive view of frailty and global (bio-psycho-social) health is strongly encouraged.