Neddylation inhibition affects early embryonic development by disrupting maternal-to-zygotic transition and mitochondrial function in mice.

Post-translational modifications (PTMs) are critical for early development in mice because early cleavage-stage embryos are characterized by transcriptional inactivity. Neddylation is an important ubiquitin-like PTM that regulates multiple biophysical processes. However, the exact roles of neddylation in regulating early embryonic development remain largely unknown. In the present study, we found that inhibition of neddylation by specific inhibitor MLN4924 led to severe arrest of early embryonic development. Transcriptomic analysis showed that neddylation inhibition changed the expression of 3959 genes at the 2-cell stage. Importantly, neddylation inhibition blocked zygotic genome activation and maternal mRNA degradation, thus disrupting the maternal-to-zygotic transition. Moreover, inhibition of neddylation induced mitochondrial dysfunction including aberrant mitochondrial distribution, decreased mitochondrial membrane potential, and reduced ATP content. Further analysis showed that inhibition of neddylation resulted in the accumulation of reactive oxygen species and superoxide anion, thereby resulting in oxidative stress and severe DNA damage at the 2-cell stage. Overall, this study demonstrates that neddylation is vital for early embryonic development in mice. Our findings suggest that proper neddylation regulation is essential for the timely inter-stage transition during early embryonic development.

Posttraumatic stress disorder symptoms and posttraumatic growth among college students with a history of childhood maltreatment in China: A latent profile analysis.

BACKGROUND: Childhood maltreatment is prevalent in China, and research indicates that trauma-exposed individuals may exhibit concurrent negative and positive posttraumatic psychological responses. OBJECTIVE: To examine the co-occurring patterns of posttraumatic stress disorder (PTSD) symptoms and posttraumatic growth (PTG) among college students in China having a history of childhood maltreatment. METHOD: Participants (N = 2,968) were college students from China who had experienced childhood maltreatment and had completed the PTSD Checklist, a PTG inventory, and a childhood maltreatment questionnaire. RESULTS: The results revealed four heterogeneous profiles characterized by low symptoms (n = 666, 22.4%), growth (n = 960, 32.3%), struggle (n = 1,285, 43.3%), and distress (n = 57, 1.9%). The three-step approach revealed emotional abuse and sexual abuse as crucial risk factors for the distress profile. In addition, age, sex, parental education, and forms of childhood maltreatment play distinctive roles in the four profiles of posttraumatic reactions. CONCLUSION: Posttraumatic reactions exhibit heterogeneous characteristics among Chinese college students exposed to childhood maltreatment, and professionals provide the service targeting their needs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Requirement of microtubules for secretion of a micronemal protein CpTSP4 in the invasive stage of the apicomplexan Cryptosporidium parvum.

The zoonotic Cryptosporidium parvum is a global contributor to infantile diarrheal diseases and opportunistic infections in immunocompromised or weakened individuals. Like other apicomplexans, it possesses several specialized secretory organelles, including micronemes, rhoptry, and dense granules. However, the understanding of cryptosporidial micronemal composition and secretory pathway remains limited. Here, we report a new micronemal protein in C. parvum, namely, thrombospondin (TSP)-repeat domain-containing protein-4 (CpTSP4), providing insights into these ambiguities. Immunostaining and enzyme-linked assays show that CpTSP4 is prestored in the micronemes of unexcysted sporozoites but secreted during sporozoite excystation, gliding, and invasion. In excysted sporozoites, CpTSP4 is also distributed on the two central microtubules unique to Cryptosporidium. The secretion and microtubular distribution could be completely blocked by the selective kinesin-5 inhibitors SB-743921 and SB-715992, resulting in the accumulation of CpTSP4 in micronemes. These support the kinesin-dependent microtubular trafficking of CpTSP4 for secretion. We also localize γ-tubulin, consistent with kinesin-dependent anterograde trafficking. Additionally, recombinant CpTSP4 displays nanomolar binding affinity to the host cell surface, for which heparin acts as one of the host ligands. A novel heparin-binding motif is identified and validated biochemically for its contribution to the adhesive property of CpTSP4 by peptide competition assays and site-directed mutagenesis. These findings shed light on the mechanisms of intracellular trafficking and secretion of a cryptosporidial micronemal protein and the interaction of a TSP-family protein with host cells.IMPORTANCECryptosporidium parvum is a globally distributed apicomplexan parasite infecting humans and/or animals. Like other apicomplexans, it possesses specialized secretory organelles in the zoites, in which micronemes discharge molecules to facilitate the movement and invasion of zoites. Although past and recent studies have identified several proteins in cryptosporidial micronemes, our understanding of the composition, secretory pathways, and domain-ligand interactions of micronemal proteins remains limited. This study identifies a new micronemal protein, namely, CpTSP4, that is discharged during excystation, gliding, and invasion of C. parvum sporozoites. The CpTSP4 secretion depends on the intracellular trafficking on the two Cryptosporidium-unique microtubes that could be blocked by kinesin-5/Eg5 inhibitors. Additionally, a novel heparin-binding motif is identified and biochemically validated, which contributes to the nanomolar binding affinity of CpTSP4 to host cells. These findings indicate that kinesin-dependent microtubular trafficking is critical to CpTSP4 secretion, and heparin/heparan sulfate is one of the ligands for this micronemal protein.

Augmented feedback modes during functional grasp training with an intelligent glove and virtual reality for persons with traumatic brain injury.

Introduction: Physical therapy is crucial to rehabilitating hand function needed for activities of daily living after neurological traumas such as traumatic brain injury (TBI). Virtual reality (VR) can motivate participation in motor rehabilitation therapies. This study examines how multimodal feedback in VR to train grasp-and-place function will impact the neurological and motor responses in TBI participants (n = 7) compared to neurotypicals (n = 13). Methods: We newly incorporated VR with our existing intelligent glove system to seamlessly enhance the augmented visual and audio feedback to inform participants about grasp security. We then assessed how multimodal feedback (audio plus visual cues) impacted electroencephalography (EEG) power, grasp-and-place task performance (motion pathlength, completion time), and electromyography (EMG) measures. Results: After training with multimodal feedback, electroencephalography (EEG) alpha power significantly increased for TBI and neurotypical groups. However, only the TBI group demonstrated significantly improved performance or significant shifts in EMG activity. Discussion: These results suggest that the effectiveness of motor training with augmented sensory feedback will depend on the nature of the feedback and the presence of neurological dysfunction. Specifically, adding sensory cues may better consolidate early motor learning when neurological dysfunction is present. Computerized interfaces such as virtual reality offer a powerful platform to personalize rehabilitative training and improve functional outcomes based on neuropathology.

Exploring gender differences in the relationships among childhood maltreatment, PTSD, and depression in young adults through network analysis.

BACKGROUND AND OBJECTIVES: College students who have experienced childhood maltreatment commonly exhibit adverse psychological consequences such as post-traumatic stress disorder (PTSD) and depression. The aim of this study is to use network analysis to investigate the gender differences in complex connections among various types of childhood maltreatment, PTSD, and depression. METHODS: This study involved 481 participants (M = 19.25 years, 54.5 % female) who were selected from a larger sample of 5231 college students. These participants had experienced childhood maltreatment and exhibited significant clinical symptoms of PTSD and depression. The participants completed validated measures that assessed childhood trauma, PTSD, and depression. RESULTS: The network analysis performed on the entire sample revealed robust connections among various types of childhood maltreatment, symptom clusters of PTSD, and depression. The most central symptom that emerged was negative alterations in cognitions and mood (NACM), with emotional abuse displaying the highest centrality measure among the various types of childhood maltreatment. Upon comparing the subnetworks, the centrality analysis identified significant gender differences in nodes such as sexual abuse, physical neglect, emotional neglect, and avoidance. CONCLUSIONS: The study's findings confirm that various forms of childhood abuse have intricate and multifaceted connections with depression and PTSD symptoms in adulthood. The study suggests that NACM could be the most significant symptom, and emotional abuse may play a vital role in adverse psychological outcomes. Furthermore, notable gender discrepancies were identified in the relationship between various forms of maltreatment and psychopathological symptoms.

Cost-effective In Vivo and In Vitro Mouse Models for Evaluating Anticryptosporidial Drug Efficacy: Assessing Vorinostat, Docetaxel, and Baicalein.

BACKGROUND: Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo. METHODS: Cryptosporidium tyzzeri, a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis, was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model. RESULTS: Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri. CONCLUSIONS: Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.

Lactational exposure to Deoxynivalenol causes mammary gland injury via inducing inflammatory response and impairing blood-milk barrier integrity in mice.

Lactation is a unique physiological process to produce and secrete milk. Deoxynivalenol (DON) exposure during lactation has been demonstrated to affect adversely the growth development of offspring. However, the effects and potential mechanism of DON on maternal mammary glands remain largely unknown. In this study, we found the length and area of mammary glands were significantly reduced after DON exposure on lactation day (LD) 7 and LD 21. RNA-seq analysis results showed that the differentially expressed genes (DEGs) were significantly enriched in acute inflammatory response and HIF-1 signaling pathway, which led to an increase of myeloperoxidase activity and inflammatory cytokines. Furthermore, lactational DON exposure increased blood-milk barrier permeability by reducing the expression of ZO-1 and Occludin, promoted cell apoptosis by upregulating the expression of Bax and cleaved Caspase-3 and downregulating the expression of Bcl-2 and PCNA. Additionally, lactational DON exposure significantly decreased serum concentration of prolactin, estrogen, and progesterone. All these alterations eventually resulted in a decrease of ß-casein expression on LD 7 and LD 21. In summary, our findings indicated that lactational exposure to DON caused lactation-related hormone disorder and mammary gland injury induced by inflammatory response and blood-milk barrier integrity impairment, ultimately resulting in lower production of ß-casein.

The reciprocal relations among self-compassion, posttraumatic stress disorder, and posttraumatic growth among adolescents after the Jiuzhaigou earthquake: a three-wave cross-lagged study.

BACKGROUND: Previous cross-sectional studies have examined the relationship between self-compassion, post-traumatic stress disorder (PTSD), and post-traumatic growth (PTG). But no study has tested whether self-compassion is a cause or a consequence of PTSD, PTG, or both. AIMS: The cross-lag analysis was used to examine the reciprocal effects among self-compassion, PTSD, and PTG. METHOD: We used data from 244 adolescents who had experienced earthquakes. We assessed self-compassion, PTSD, and PTG via self-report measures after the earthquake in Jiuzhaigou, as well as 6 and 12 months later. RESULTS: Cross-lagged analyses indicated that positive self-compassion could significantly predict subsequent PTSD and PTG. Meanwhile, PTSD and PTG also predicted later positive self-compassion. Negative self-compassion at T1 increased PTSD at T2, and neither PTSD nor PTG significantly predicted subsequent negative self-compassion. In addition, negative self-compassion at T1 significantly predicted positive self-compassion at T2, while positive self-compassion at T2 significantly predicted negative self-compassion at T3. CONCLUSIONS: Positive self-compassion is a protective factor of post-traumatic psychological response, and it is maintained for a long time, while negative self-compassion may aggravate the negative psychological outcomes of adolescents in the early stage of experiencing traumatic events. In addition, positive and negative self-compassion can influence each other over time.

The reciprocal relations among self-compassion, and depression among adolescents after the Jiuzhaigou earthquake: A three-wave cross-lagged study.

BACKGROUND: Previous cross-sectional studies have examined the relationship between self-compassion and depression. Although it is often implicitly assumed that self-compassion may increase the vulnerability of an individual to depression, only a few studies have assessed whether self-compassion is a cause or a consequence of depression or both. METHOD: To examine such reciprocal effects, we assessed self-compassion and depression via self-report measures. At the baseline assessment (Time 1, T1), 450 students (M = 13.72, SD = 0.83, 54.2% females) participated 10 months after the Jiuzhaigou earthquake. We reassessed the T1 sample after 6- and 12-month intervals. At Time 2 (T2) assessment, 398 (56.0% female participants) of the Wave 1 participants were retained, and at Time 3 (T3) assessment, 235 (52.5% female participants) of the T1 and T2 participants were retained. RESULTS: Cross-lagged analyses indicated that positive self-compassion could significantly reduce subsequent depression. However, depression did not significantly predict later positive self-compassion. Negative self-compassion at T1 increased depression at T2, but negative self-compassion at T2 did not significantly predict depression at T3. In addition, positive self-compassion significantly reduced subsequent negative self-compassion. CONCLUSIONS: Positive self-compassion appears to protect adolescents against depression and maintain this protection over time, whereas negative self-compassion may worsen depression in adolescents during the initial stages of traumatic events. Additionally, positive self-compassion may decrease the level of negative self-compassion.

Effects of IL-11/IL-11 Receptor Alpha on Proliferation and Steroidogenesis in Ovarian Granulosa Cells of Dairy Cows.

Granulosa cells (GCs) are essential for follicular growth, oocyte maturation, and steroidogenesis in the ovaries. Interleukin (IL)-11 is known to play a crucial role in the decidualization of the uterus, however, the expression of the IL-11 system (IL-11, IL-11Rα, and gp130) in the bovine ovary and its exact role in GCs have not been extensively studied. In this study, we identified the IL-11 signaling receptor complex in the bovine ovary and investigated the regulatory effects and underlying mechanism of IL-11Rα on the proliferation and steroidogenesis of GCs. We observed that the IL-11 complex was highly expressed in the GCs of large follicles. IL-11Rα knockdown significantly inhibited GC proliferation by inducing cell cycle arrest at the G1 phase, along with a significant downregulation of proliferating cell nuclear antigen (PCNA) and Cyclin D1 (CCND1) protein, and induced GC apoptosis by significantly upregulating the ratio of BCL-2-associated X protein (BAX) and B-cell lymphoma-2 (BCL-2). In addition, IL-11Rα knockdown attenuated the Janus kinase (JAK) 1-signal transducer and activator of transcription 3 (STAT3) signaling, which is related to cell proliferation and apoptosis. Furthermore, the enzyme-linked immunosorbent assay (ELISA) indicated that IL-11Rα silencing decreased the basal and forskolin (FSK)-stimulated secretions of estradiol and progesterone in GC culture medium concomitantly with a remarkable decrease in cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and steroidogenic acute regulatory protein (StAR). We subsequently determined that this reduction in steroidogenesis was in parallel with the decrease in phosphorylations of protein kinase A (PKA) substrates, cAMP-response element binding protein (CREB), extracellular regulated protein kinase (ERK) 1/2, and p38 mitogen-activated protein kinase (MAPK). Taken together, these data indicate that the effects of IL-11/IL-11Rα on the proliferation and steroidogenesis in bovine GCs is mediated by the JAK1-STAT3, PKA-CREB, p38MAPK, and ERK1/2 signaling pathways. Our findings provide important insights into the local action of the IL-11 system in regulating ovarian function.

Deoxynivalenol exposure inhibits biosynthesis of milk fat and protein by impairing tight junction in bovine mammary epithelial cells.

Deoxynivalenol (DON) is one of the most common feed contaminants, and it poses a serious threat to the health of dairy cows. The existing studies of biological toxicity of DON mainly focus on the proliferation, oxidative stress, and inflammation in bovine mammary epithelial cells, while its toxicity on the biosynthesis of milk components has not been well documented. Hence, we investigated the toxic effects and the underlying mechanism of DON on the bovine mammary alveolar cells (MAC-T). Our results showed that exposure to various concentrations of DON significantly inhibited cell proliferation, induced apoptosis, and altered the cell morphology which was manifested by cell distortion and shrinkage. Moreover, the transepithelial electrical resistance (TEER) values of MAC-T cells exposed to DON were gradually decreased in a time- and concentration- dependent manner, but lactate dehydrogenase (LDH) leakage was significantly increased with the maximum increase of 2.4-fold, indicating the cell membrane and tight junctions were damaged by DON. Importantly, DON significantly reduced the synthesis of ß-casein and lipid droplets, along with the significantly decreases of phospho-mTOR, phospho-4EBP1, phospho-JAK2, and phospho-STAT5. Gene expression profiles showed that the expressions of several genes related to lipid synthesis and metabolism were changed, including acyl-CoA synthetase short-chain family member 2 (ACSS2), fatty acid binding protein 3 (FABP3), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), and insulin-induced gene 1 (INSIG1). GO and KEGG enrichment analyses revealed that the differentially expressed genes (DEGs) were significantly enriched in ribosome, glutathione metabolism, and lipid biosynthetic process, which play important roles in the toxicological process induced by DON. Taken together, DON affects the proliferation and functional differentiation of MAC-T cells, which might be related to the cell junction disruption and morphological alteration. Our data provide new insights into functional differentiation and transcriptomic alterations of MAC-T cells after DON exposure, which contributes to a comprehensive understanding of DON-induced toxicity mechanism.

Novel functional mutation of the PDIA3 gene affects milk composition traits in Chinese Holstein cattle.

Protein disulfide isomerase family A member 3 (PDIA3) is a multifunctional protein, and it plays a vital role in modulating various cell biological functions under physiological and pathological conditions. Our previous study on Mediterranean buffalo demonstrated that PDIA3 is a potential candidate gene associated with milk yield based on genome-wide association study analysis. However, the genetic effects of the PDIA3 gene on milk performance in dairy cattle and the corresponding mechanism have not been documented. This study aims to explore the genetic effects of PDIA3 polymorphisms on milk production traits in 362 Chinese Holstein cattle. The results showed that 4 SNPs were identified from the 5' untranslated region of the PDIA3 gene in the studied population, of which 2 SNPs (g.-1713 C>T and g.-934 G>A) were confirmed to be significantly associated with milk protein percentage, whereas g.-434 C>T was significantly associated with milk fat percentage. Notably, linkage disequilibrium analysis indicated that 3 SNPs (g.-1713 C>T, g.-934 G>A, and g.-695 A>C) formed one haplotype block, which was found to be significantly associated with milk protein percentage. The luciferase assay demonstrated that allele C of g.-434 C>T exhibited a higher promotor activity compared with allele T, suggesting that g.-434 C>T might be a potential functional mutation affecting PDIA3 expression. Furthermore, overexpression of the PDIA3 gene was found to induce higher levels of triglyceride and BODIPY fluorescence intensity. In addition, PDIA3 overexpression was also found to positively regulate the synthesis and secretion of α-casein, ß-casein, and κ-casein, whereas knockdown of this gene showed the opposite effects. In summary, our findings revealed significant genetic effects of PDIA3 on milk composition traits, and the identified SNP and the haplotype block might be used as genetic markers for dairy cow selected breeding.

From Mouth to Brain: Distinct Supragingival Plaque Microbiota Composition in Cerebral Palsy Children With Caries.

Children with cerebral palsy (CP) present a higher prevalence and severity of caries. Although researchers have studied multiple risk factors for caries in CP, the role of microorganisms in caries remains one of the critical factors worth exploring. In order to explore the differences in the supragingival plaque microbiota (SPM), supragingival plaque samples were collected from 55 CP children and 23 non-CP children for 16S rRNA sequencing. Distinct SPM composition was found between CP children with severe caries (CPCS) and non-CP children with severe caries (NCPCS). Further subanalysis was also done to identify if there were any differences in SPM among CP children with different degrees of caries, namely, caries-free (CPCF), mild to moderate caries (CPCM), and severe caries (CPCS). After selecting the top 15 most abundant species in all groups, we found that CPCS was significantly enriched for Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, Porphyromonas endodontalis, Catonella morbi, Alloprevotella tannerae, Parvimonas micra, Streptobacillus moniliformis, and Porphyromonas canoris compared to NCPCS. By comparing CPCF, CPCM, and CPCS, we found that the core caries-associated microbiota in CP children included Prevotella, Alloprevotella, Actinomyces, Catonella, and Streptobacillus, while Capnocytophaga and Campylobacter were dental health-associated microbiota in CP children. Alpha diversity analysis showed no significant difference between NCPCS and CPCS, but the latter had a much simpler core correlation network than that of NCPCS. Among CP children, CPCM and CPCF displayed lower bacterial diversity and simpler correlation networks than those of CPCS. In summary, the study showed the specific SPM characteristics of CPCS compared to NCPCS and revealed the core SPM in CP children with different severities of caries (CPCF, CPCM, and CPCS) and their correlation network. Hopefully, the study would shed light on better caries prevention and therapies for CP children. Findings from the current study offer exciting insights that warrant larger cohort studies inclusive of saliva and feces samples to investigate the potential pathogenic role of oral microbiota through the oral-gut-brain axis in CP children with caries.

Hand dominance in the performance and perceptions of virtual reach control.

PURPOSE: Efforts to optimize human-computer interactions are becoming increasingly prevalent, especially with virtual reality (VR) rehabilitation paradigms that utilize engaging interfaces. We hypothesized that motor and perceptional behaviors within a virtual environment are modulated uniquely through different modes of control of a hand avatar depending on limb dominance. This study investigated the effects of limb dominance on performance and concurrent changes in perceptions, such as time-based measures for intentional binding, during virtual reach-to-grasp. METHODS: Participants (n = 16, healthy) controlled a virtual hand through their own hand motions with control adaptations in speed, noise, and automation. RESULTS: A significant (p < 0.01) positive relationship between performance (reaching pathlength) and binding (time-interval estimation of beep-sound after grasp contact) was observed for the dominant hand. Unique changes in performance (p < 0.0001) and binding (p < 0.0001) were observed depending on handedness and which control mode was applied. CONCLUSIONS: Developers of VR paradigms should consider limb dominance to optimize settings that facilitate better performance and perceptional engagement. Adapting VR rehabilitation for handedness may particularly benefit unilateral impairments, like hemiparesis or single-limb amputation.

Host cells with transient overexpression of MDR1 as a novel in vitro model for evaluating on-target effect for activity against the epicellular Cryptosporidium parasite.

OBJECTIVES: To rapidly generate host cells with resistance to multiple compounds for differentiating drug action on parasite target or the host cell target (i.e. on-target or off-target effect) against the zoonotic enteric parasite Cryptosporidium parvum. METHODS: Transient overexpression of a multidrug resistance protein 1 (MDR1) gene in host cells (HCT-8 cell line) was explored to increase drug tolerance of the host cells to selected anti-cryptosporidial leads. In vitro cytotoxicity and anti-cryptosporidial efficacy of selected compounds were evaluated on the parasite grown in WT parental and transiently transfected HCT-8 cells. The approach was based on the theory that, for an epicellular parasite receiving consistent exposure to compounds in culture medium, overexpressing MDR1 in HCT-8 cells would increase drug tolerance of host cells to selected compounds but would not affect the anti-cryptosporidial efficacy if the compounds acted solely on the parasite target and the drug action on host cell target played no role on the antiparasitic efficacy. RESULTS: Six known anti-cryptosporidial leads were tested. Transient overexpression of MDR1 increased drug tolerance of HCT-8 cells on paclitaxel, doxorubicin HCl and vincristine sulphate (2.11- to 2.27-fold increase), but not on cyclosporin A, daunorubicin HCl and nitazoxanide. Increased drug tolerance in host cells had no effect on antiparasitic efficacy of paclitaxel, but affected that of doxorubicin HCl. CONCLUSIONS: Data confirmed that, at efficacious concentrations, paclitaxel acted mainly on the parasite target, while doxorubicin might act on both parasite and host cell targets. This model can be employed for studying the action of additional anti-cryptosporidial leads, and adapted to studying drug action in other epicellular pathogens. The limitation of the model is that the anti-cryptosporidial leads/hits need to be MDR1 substrates.

The Association between Obesity and Severity in Patients with Coronavirus Disease 2019: a Retrospective, Single-center Study, Wuhan.

Aim: In other respiratory infectious diseases, obesity may be associated with a poor outcome. For coronavirus disease 2019 (COVID-19), the association between obesity and severity or prognosis requires further analysis. Methods: This was a retrospective, single-center study. Hospitalized patients were recruited in Renmin Hospital of Wuhan University from January 2, 2020 to February 20, 2020. The data of body mass index (BMI) was obtained from follow-up of surviving patients. According to BMI, normal weight was defined as 18.5-23.9 kg/m2, overweight as 24.0-27.9 kg/m2 and obesity as > 28.0 kg/m2. Results: A total of 463 patients were enrolled, of which 242 (52.3%) patients were in the normal weight group; 179 (38.7%) were in the overweight group; and 42 (9.1%) were in the obesity group. Compared to the normal group, obese patients were more likely to have a higher heart rate; lower finger oxygen saturation; higher levels of white blood cells, neutrophil counts, basophil counts, intravenous glucose, triacylglycerol, uric acid, alanine aminotransferase, creatine kinase-MB, CD19+ cell counts and percentage; and lower levels of monocyte percentage, high density lipoprotein and CD3+ cell percentage. In addition, the proportions of hypertension (21.5% vs. 42.6%) and severe+critical illness (47.8 vs. 81.0 %) were significantly higher in the obesity group than those in normal group. However, no significant differences were observed between the normal and obesity groups in critical illness, organ damage and defined endpoint (mechanical ventilation or intensive care unit). Multiple logistic regression showed that obesity increased the risk of developing severe+critical illness (Odd ratio 3.586, 95% CI 1.550-8.298, P=0.003) in patients with COVID-19, and did not affect the risk of critical illness, organ damage and endpoints. Overweight did not affect the risk of severity, organ damage or endpoint in patients with COVID-19. Conclusion: Obesity may be a risk factor for developing severity in patients with COVID-19.

Concurrent Continuous Versus Bandwidth Visual Feedback With Varying Body Representation for the 2-Legged Squat Exercise.

CONTEXT: Continuous visual feedback (VF) can improve abilities to achieve desired movements and maximize rehabilitation outcomes by displaying actual versus target body positions in real time. Bandwidth VF reduces the reliance on feedback by displaying movement cues only when performance errors exceed specified thresholds. As such, bandwidth VF may better train independent movement abilities through greater development of intrinsic body control. In this study, continuous and bandwidth VF were investigated across modes of display (abstract and representative) that differed in body-discernibility. OBJECTIVE: To compare the performance of the 2-legged squat during training with concurrent feedback (real-time VF) and short-term retention (immediately after training, VF removed). DESIGN: Cross-sectional. SETTING: University research laboratory. PARTICIPANTS: Eighteen healthy individuals. METHODS: Marker-based motion capture displayed real-time position. MAIN OUTCOME MEASURES: Four VF cases (continuous-abstract, bandwidth-abstract, continuous-representative, and bandwidth-representative) were evaluated for accuracy and consistency to a target trajectory and target depth. RESULTS: During training, both continuous VF cases showed significantly (P < .05) higher accuracy and consistency to the target trajectory compared with both bandwidth VF cases. Bandwidth VF resulted in greater potential learning (retention performance relative to a training baseline) compared with continuous-abstract. CONCLUSIONS: Continuous-representative may offer unique performance benefits in both training and retention of multisegment movement tasks. Bandwidth VF showed greater potential for learning. For long-term learning, an optimal VF paradigm should consider continuous-representative with bandwidth features.

Training with Agency-Inspired Feedback from an Instrumented Glove to Improve Functional Grasp Performance.

Sensory feedback from wearables can be effective to learn better movement through enhanced information and engagement. Facilitating greater user cognition during movement practice is critical to accelerate gains in motor function during rehabilitation following brain or spinal cord trauma. This preliminary study presents an approach using an instrumented glove to leverage sense of agency, or perception of control, to provide training feedback for functional grasp. Seventeen able-bodied subjects underwent training and testing with a custom-built sensor glove prototype from our laboratory. The glove utilizes onboard force and flex sensors to provide inputs to an artificial neural network that predicts achievement of "secure" grasp. Onboard visual and audio feedback was provided during training with progressively shorter time delay to induce greater agency by intentional binding, or perceived compression in time between an action (grasp) and sensory consequence (feedback). After training, subjects demonstrated a significant reduction (p < 0.05) in movement pathlength and completion time for a functional task involving grasp-move-place of a small object. Future work will include a model-based algorithm to compute secure grasp, virtual reality immersion, and testing with clinical populations.

Negative Emotions and Job Burnout in News Media Workers: A Moderated Mediation Model of Rumination and Empathy.

News media workers are in stressful and competitive professions susceptible to negative emotions. Although the relationship between negative emotions and job burnout has been evidenced in some professional fields, it has not yet been examined in the population of news media workers. Far few studies have revealed the mediating and moderating mechanism between negative emotions and job burnout. Based on Resource Allocation Theory and Theory of Compassion Fatigue, this study examined (a) the mediating role of rumination in the relationship between negative emotions and job burnout, (b) the moderating role of empathy in the direct and indirect effect of negative emotions on job burnout, and (c) the moderating role of gender in the direct effect of negative emotions on rumination. Two hundred and eleven Chinese news media workers filled out questionnaires regarding negative emotions, job burnout, rumination, and empathy. The results indicated that negative emotions were positively correlated with job burnout. Mediation analysis revealed that rumination partially mediated the association between negative emotions and job burnout. Moderated mediation analysis further indicated that empathy moderated the effect of negative emotions on rumination, with a high level of empathy strengthening the association between negative emotions and rumination; gender moderated the effect of negative emotions on rumination, with the association between negative emotions and rumination was stronger among males than females. These findings encourage to design psychological interventions to reduce rumination and express proper empathy in the face of stress or negative affective status to avoid job burnout among news media workers.

Effects of Visual Feedback Complexity on the Performance of a Movement Task for Rehabilitation.

This study investigated the effects of visual feedback (VF) complexity on movement performance to potentially optimize the design of VF-based rehabilitation. We evaluated the effects of VF complexity on performance of the two-legged squat during training with concurrent (real-time) VF and short-term retention with no VF. Four VF cases were employed to train spatial positioning of the thigh segment in unique combinations of complexity (simple, complex) and representation of body-discernibility (abstract, representative). Eighteen able-bodied subjects attempted to minimize the error between individual body segment positions and a target trajectory during concurrent VF and short-term retention tests. Complex-representative VF demonstrated greater potential for training with increased performance consistency in both motion and muscle activity patterns.