Half body irradiation (HBI) for bone metastases in the modern radiotherapy technique era - A systematic review.

Bone metastases (BMs) are the most common cause of cancer-related pain and radiation therapy plays a key role in treating pain caused by it. The half-body irradiation (HBI) is a modality that can be used to treat patients with multiple painful BMs. In the modern era, concerns about toxicity and the availability of new agents requiring robust bone marrow function have limited the use of HBI in advanced cancer. Concerns about HBI toxicity stem from outdated techniques; modern methods like volumetric modulated arc therapy (VMAT) and helical tomotherapy now allow safer irradiation of complex target volumes. We conducted a systematic review to present updated information about HBI efficacy and potential toxicity. Pain relief usually occurs very quickly 2-3 weeks after HBI. The overall pain response rate was high in all the series, accounting for a median of 84 % (75.6-89 %), with a median of 36 % complete pain response. The toxicity is usually limited to G1/G2, with very rare G3 cases. More than 50 % of patients can reduce analgesic intake after HBI. Additionally, with modern radiotherapy techniques, quality of life is improved in most patients. HBI is a safe and effective method and should once again be reconsidered for more frequent use.

HBI-8000 improves heart failure with preserved ejection fraction via the TGF-ß1/MAPK signalling pathway.

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of total heart failure patients and is characterized by peripheral circulation, cardiac remodelling and comorbidities (such as advanced age, obesity, hypertension and diabetes) with limited treatment options. Chidamide (HBI-8000) is a domestically produced benzamide-based histone deacetylase isoform-selective inhibitor used for the treatment of relapsed refractory peripheral T-cell lymphomas. Based on our in vivo studies, we propose that HBI-8000 exerts its therapeutic effects by inhibiting myocardial fibrosis and myocardial hypertrophy in HFpEF patients. At the cellular level, we found that HBI-8000 inhibits AngII-induced proliferation and activation of CFs and downregulates the expression of fibrosis-related factors. In addition, we observed that the HFpEF group and AngII stimulation significantly increased the expression of TGF-ß1 as well as phosphorylated p38MAPK, JNK and ERK, whereas the expression of the above factors was significantly reduced after HBI-8000 treatment. Activation of the TGF-ß1/MAPK pathway promotes the development of fibrotic remodelling, and pretreatment with SB203580 (p38MAPK inhibitor) reverses this pathological change. In conclusion, our data suggest that HBI-8000 inhibits fibrosis by modulating the TGF-ß1/MAPK pathway thereby improving HFpEF. Therefore, HBI-8000 may become a new hope for the treatment of HFpEF patients.

Rapid assessment of malnutrition based on GLIM diagnosis in Crohn's disease.

Background and aims: Malnutrition is strongly linked to adverse outcomes in patients with Crohn's disease (CD). In this study, our objective was to validate the Global Leadership Initiative on Malnutrition (GLIM) criteria and develop a fast and accurate diagnostic approach for identifying malnutrition in CD patients. Methods: This study assessed 177 CD patients from four general hospitals. The efficacy of the GLIM criteria for the diagnosis of CD malnutrition was compared. By analyzing the independent factors, a nomogram model was derived and internally validated to predict the diagnosis of malnutrition in patients with CD. Model performance was assessed using discrimination and calibration, decision curves, and net benefit analyses. Results: Compared with the SGA criteria, the GLIM criteria was consistent in sensitivity (88.89%) and specificity (78.43%) [AUC = 0.84; 95% Confidence Interval (CI): 0.77-0.89]. The Harvey-Bradshaw index(HBI) score (OR: 1.58; 95% CI: 1.15-2.18), body mass index (OR: 0.41; 95% CI: 0.27-0.64), and mid-upper arm circumference (OR: 0.68; 95% CI: 0.47-0.9) were independent factors associated with malnutrition. The nomogram was developed based on these indicators showing good discrimination in malnutrition diagnosis (AUC = 0.953; 95% CI: 0.922-0.984), with agreement after calibration curve and decision curve analysis. Conclusion: The GLIM criteria are appropriate for diagnosing malnutrition in CD patients. The HBI score may be used to diagnose malnutrition in patients with CD and become a possible selection for the GLIM etiologic criteria of inflammation. The HBM nomogram could be a simple, rapid, and efficient method for diagnosing malnutrition in CD patients.

A new form of neurotherapy for a patient with anxiety disorder and anomic aphasia after neurosurgery for a ruptured brain aneurysm post-COVID-19.

INTRODUCTION AND OBJECTIVE: The aim of this study is to evaluate the effectiveness of a new, neuromarker-based form of neurotherapy for a patient with anxiety disorders and anomic aphasia after a neurosurgical operation for a ruptured brain aneurysm of the left middle cerebral artery (MCA), detected after COVID-19. CASE REPORT: A 78-year-old right-handed patient, not previously treated for any chronic diseases except stage II hypertension, contracted COVID-19, confirmed by real time RT- PCR. He was treated on an outpatient basis. Two months later, he developed an unusually severe headache and disorientation. A ruptured brain aneurysm of the left MCA was diagnosed. The patient underwent a neurosurgical operation - clipping- very well, with no neurological or neuropsychiatric disorders, except for mild aphasia and occasional anxiety attacks. Four weeks after surgery, anxiety disorder and mild aphasia worsened. High levels of anxiety on the Hospital Anxiety and Depression (HAD) Scale, and mild anomic aphasia in the Boston Naming Test (BNT) was found. A functional neuromarker of anxiety in comparision to a normative database (Human Brain Index, HBI) was detected. The patient was offered a new, neuromarker-based form of neurotherapy, which proved effective in reducing the disorders. The patient improved in social communication and is gradually returning to social activities. CONCLUSION: In patients with anxiety disorders, anomic aphasia and related difficulties in social functioning after aSAH, especially after COVID-19, multidimensional diagnosis and therapy, preferably based on functional neuromarkers, is needed. HBI methodology can be successfully used in the neurodiagnosis and implementation of individualized neurotherapy for such patients.

Modulation of Allosteric Control and Evolution of Hemoglobin.

Allostery arises when a ligand-induced change in shape of a binding site of a protein is coupled to a tertiary/quaternary conformational change with a consequent modulation of functional properties. The two-state allosteric model of Monod, Wyman and Changeux [J. Mol. Biol. 1965; 12, 88-118] is an elegant and effective theory to account for protein regulation and control. Tetrameric hemoglobin (Hb), the oxygen transporter of all vertebrates, has been for decades the ideal system to test for the validity of the MWC theory. The small ligands affecting Hb's behavior (organic phosphates, protons, bicarbonate) are produced by the red blood cell during metabolism. By binding to specific sites, these messengers make Hb sensing the environment and reacting consequently. HbI and HbIV from trout and human HbA are classical cooperative models, being similar yet different. They share many fundamental features, starting with the globin fold and the quaternary assembly, and reversible cooperative O2 binding. Nevertheless, they differ in ligand affinity, binding of allosteric effectors, and stability of the quaternary assembly. Here, we recollect essential functional properties and correlate them to the tertiary and quaternary structures available in the protein databank to infer on the molecular basis of the evolution of oxygen transporters.

Agreement between patients and physicians on scores of inflammatory bowel disease activity and burden assessed on a telemonitoring platform.

BACKGROUND AND AIMS: Telemonitoring is increasingly used in the management of IBD patients. We investigated the agreement between patients and physicians on scores of disease activity and burden. METHODS: Consecutive outpatients at one IBD clinic were recruited between February and December 2021. Enrolled patients completed a questionnaire for disease activity (Harvey-Bradshaw Index [HBI] for Crohn's disease or Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis) and a test of disease burden (Pictorial Representation of Illness and Self Measure [PRISM]). They did the tests within 5 days of an outpatient visit, working independently on IBD Tool, a new web-based telemonitoring application. Concomitantly, the senior and junior physicians who examined them completed the same tests. The agreement was tested for every pair of scores. RESULTS: Five hundred and sixty patients (289 Crohn's disease; 271 ulcerative colitis) completed disease questionnaires on IBD Tool (in total, 742 times). By Spearman's correlation, the agreement was substantial both for HBI (rho 0.685-0.837) and SCCAI (rho 0.694-0.888) for comparisons between patients, junior and senior physicians. The agreement was moderate-to-substantial for PRISM (rho 0.406-0.725) for the same comparisons. The correlation between disease activity (HBI/SCCAI) and PRISM scores was substantial for senior (rho 0.757-0.788) or junior (rho 0.746-0.753) physicians and moderate for patients (rho 0.458-0.486). The median PRISM score difference was 2.3-1.6 points lower between patients and senior-junior physicians. CONCLUSION: Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease impact. The inclusion of disease burden scoring in telemonitoring platforms provides important information for the management of IBD patients.Study highlightsWhat IS known•Continuous response to treatments and patient-reported outcomes became an essential goal for IBD patient management.•The use of tele-monitoring and eHealth technologies allows for regular disease assessments and for managing more efficiently IBD patients; disease questionnaires and tests are key to support eHealth tools.What is new here•Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease burden, while agreement among junior and senior physicians was substantial for both.•PRISM performs as well for ulcerative colitis as for Crohn's patients.•The inclusion of disease burden tests might add to eHealth platforms valuable information, complemental to disease activity questionnaires.

Predicting Mucosal Healing in Crohn's Disease: A Nomogram Model Developed from a Retrospective Cohort.

Purpose: Mucosal healing (MH) has become a therapeutic end point for Crohn's disease (CD). The purpose of this study was to identify potential risk factors responsible for a lower probability of mucosal healing in CD. It also aimed to create and validate a noninvasive tool for predicting mucosal healing in CD to aid clinical decision-making. Patients and Methods: We established a derivation cohort diagnosed with CD, in which endoscopic examination was performed before and after treatment at the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021. Patient data including demographic and clinical characteristics and treatment details were collected. The achievement of mucosal healing (without ulceration on endoscopic examination) after treatment was the endpoint observed during follow-up. We performed logistic regression analysis to identify factors associated with mucosal healing. These factors were used to develop a model (CD mucosal healing prediction nomogram) to predict mucosal healing in CD. External validation was performed using a new cohort of 60 patients from the Second Affiliated Hospital of Soochow University between January 2012 and June 2021. Results: A total of 331 patients were included in the derivation cohort. We found the following factors to be independently associated with mucosal healing after treatment: disease course <11 months, ulcer size <0.5 cm, Harvey-Bradshaw Index score <9, infliximab treatment, and non-exclusive use of 5-aminosalicylic acid. The model incorporating these factors achieved good discrimination, calibration, and clinical decision curve analysis results on internal validation (C-index: 0.788, 95% confidence interval [CI]: 0.74-0.84). The external validation cohort also demonstrated good discrimination (C-index: 0.785, 95% CI: 0.68-0.90) and calibration. Conclusion: The CD mucosal healing prediction nomogram model demonstrated good reliability and validated. It can potentially be developed into a simple and clinically useful tool for predicting mucosal healing in CD.

The Intensity of the Health Behaviors of People Who Practice Wheelchair Basketball, Wheelchair Rugby and Para-Rowing.

Sports serve people with disabilities as a form of rehabilitation. Sporting activity is a health-promoting behavior choice and a chance to achieve the best possible sports results. The aim of this study was to evaluate the intensity of health behaviors in people practicing wheelchair basketball, wheelchair rugby and para-rowing. The study encompassed 176 athletes with disabilities, aged 19 to 49 (mean age 34.41 ± 8.56), from all over Poland. Men accounted for 83.5% of the respondents. They all had a significant degree of disability and used wheelchairs in their daily lives. The authors used Juczynski's Health Behavior Inventory (HBI) and the authors' own survey questionnaire. Nonparametric tests were used. A greater intensity of health behaviors in general (HBI­point score) and in four categories (correct eating habits­CEH, preventive behaviors­PB, positive mental attitude­PMA, health practices­HP) was observed in rugby and basketball players (compared with para-rowers). Disabled rowers achieved the poorest results. Polish Champions scored better results in preventive behaviors (PB) and weaker results in positive mental attitude (PMA)compared with those practicing amateur sport. Respondents who trained every day and had the longest weekly exercise time (>360 min) achieved the highest results in HBI in general and in all categories compared with those who trained once a week for less than 120 min a week. Respondents with higher education, those in a better financial situation, those who were employed and married, and those who were rural residents displayed a greater intensity of health-related behaviors. People in a more difficult financial situation, who had less education, who were cohabiting, and who lived on only a pension presented more preventive behaviors. There is a need for systemic health education aimed at people with disabilities who practice various sports disciplines.

Oral histone deacetylase inhibitor HBI-8000 (tucidinostat) in Japanese patients with relapsed or refractory non-Hodgkin's lymphoma: phase I safety and efficacy.

OBJECTIVE: HBI-8000 (tucidinostat) is a novel, oral histone deacetylase inhibitor that selectivity inhibits Class I (histone deacetylase 1, 2, 3) and Class II (histone deacetylase 10) with direct anti-tumor activity through various mechanisms of action, including epigenetic reprogramming and immunomodulation. It has been approved in China for the treatment of relapsed or refractory peripheral T-cell lymphoma. METHODS: This multicenter, prospective phase I dose-escalation trial evaluating the safety of twice weekly HBI-8000 was conducted in Japan. Eligible patients had non-Hodgkin's lymphoma and no available standard therapy. The primary endpoint was maximum tolerated dose; secondary endpoints included anti-tumor activity, safety and pharmacokinetics. RESULTS: Fourteen patients were enrolled in the study. Twelve patients were assessed for dose-limiting toxicity: six patients in the 30 mg BIW cohort had no dose-limiting toxicitys; two of six patients in the 40 mg BIW cohort had asymptomatic dose-limiting toxicitys. Treatment was well tolerated; adverse events were predominantly mild to moderate hematologic toxicities and were managed with dose modification and supportive care. Thirteen patients were included in the efficacy analysis. Objective response was seen in five of seven patients in the 40 mg BIW cohort; three partial responders had adult T-cell leukemia-lymphoma. In the 30 mg BIW cohort, three of six patients had stable disease after the first cycle. CONCLUSIONS: Treatment with HBI-8000 30 and 40 mg BIW were well-tolerated and safe, with hematological toxicities as expected from other studies of histone deacetylase inhibitor. The maximum tolerated dose and recommended dosage for phase II studies of HBI-8000 is 40 mg BIW. Preliminary efficacy results are encouraging.

Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results.

This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.

The role of the intestinal ultrasound in Crohn's disease diagnosis and monitoring.

Crohn's disease is characterized by persistent or recurrent chronic inflammation that may affect any segment of the gastrointestinal tract. It has an oscillating evolution, with periods of activity alternating with periods of remission. Crohn's disease has a significant impact on the economic status due to its increasing prevalence, often affecting young people. Suitable management for these patients involves frequent evaluations. Even though colonoscopy is the gold standard for the assessment of severity and mucosal healing, it is an invasive maneuver, not easily accepted by patients, and it does not have good repeatability. Intestinal ultrasound has the advantage of being non-irradiating, non-invasive, well-tolerated, cheap, and easy to repeat. Ultrasound parameters such as bowel wall thickness, intestinal wall architecture, intramural vascularisation, proliferation of mesenteric fatty conjunctive tissue, and intraperitoneal fluid can provide good information regarding the severity of the disease, the differentiation between remission and relapse, and its complications. Some of the latest studies show good correlations between ultrasound parameters and inflammation markers (C-reactive protein, fecal calprotectin) and clinical severity scores of Crohn's disease. Consequently, the importance of intestinal ultrasound has increased lately, and recent studies support its use to evaluate the severity of inflammation, differentiate between active disease and relapse, monitor therapy response and guide treatment, evaluate prognosis, and diagnose complications.

A transcriptional hub integrating gibberellin-brassinosteroid signals to promote seed germination in Arabidopsis.

Seed germination is regulated by multiple phytohormones, including gibberellins (GAs) and brassinosteroids (BRs); however, the molecular mechanism underlying GA and BR co-induced seed germination is not well elucidated. We demonstrated that BRs induce seed germination through promoting testa and endosperm rupture in Arabidopsis. BRs promote cell elongation, rather than cell division, at the hypocotyl-radicle transition region of the embryonic axis during endosperm rupture. Two key basic helix-loop-helix transcription factors in the BR signaling pathway, HBI1 and BEE2, are involved in the regulation of endosperm rupture. Expression of HBI1 and BEE2 was induced in response to BR and GA treatment. In addition, HBI1- or BEE2-overexpressing Arabidopsis plants are less sensitive to the BR biosynthesis inhibitor, brassinazole, and the GA biosynthesis inhibitor, paclobutrazol. HBI1 and BEE2 promote endosperm rupture and seed germination by directly regulating the GA-Stimulated Arabidopsis 6 (GASA6) gene. Expression of GASA6 was altered in Arabidopsis overexpressing HBI1, BEE2, or SRDX-repressor forms of the two transcription factors. In addition, HBI1 interacts with BEE2 to synergistically activate GASA6 expression. Our findings define a new role for GASA6 in GA and BR signaling and reveal a regulatory module that controls GA and BR co-induced seed germination in Arabidopsis.

HBI-8000, HUYABIO Lead Clinical Program, Is a Selective Histone Deacetylase Inhibitor With Therapeutic Benefits in Leukemia and in Solid Tumors.

HBI-8000 is a small molecule inhibitor of class I HDACs and has been approved for the treatment of PTCL, ATL and, in combination with exemestane, in a subpopulation of breast cancer. Given the roles of HDACs in normal and cancerous cells, there are currently multiple clinical trials, by HUYABIO International, to test the efficacy of HBI-8000 in monotherapy or in combination settings in leukemias and in solid tumors. The current review is focused on the applications of HDACi HBI-8000 in cancer therapy and its potential in combination with DDR agents.

HBI1 acts downstream of ERECTA and SWR1 in regulating inflorescence architecture through the activation of the brassinosteroid and auxin signaling pathways.

Inflorescence architecture critically influences plant reproductive success and crop yield, and it reflects the activity of the inflorescence meristem and pedicel length. In Arabidopsis thaliana, the ERECTA (ER) signaling pathway and the SWR1 chromatin remodeling complex jointly regulate inflorescence architecture by promoting the expression of the PACLOBUTRAZOL RESISTANCE (PRE) gene family. However, how PREs regulate inflorescence architecture remains unclear. RNA-sequencing and chromatin immunoprecipitation coupled with quantitative PCR analyses were performed. Genetic interactions between HOMOLOG OF BEE2 INTERACTING WITH IBH1 (HBI1) and the SWR1-ER-MPK6 pathway in the control of inflorescence architecture were further studied. The present findings support that HBI1 functions downstream of PREs in the SWR1 and ER pathways to regulate inflorescence architecture by promoting pedicel elongation. Specifically, it binds to the promoters of the brassinosteroid (BR) biosynthesis gene CYP85A2 and a series of auxin-related genes, including auxin response factor ARF3, and promotes their expression. In turn, ARF3 can also bind to auxin signaling genes as well as CYP85A2 to activate their expression and promote pedicel elongation. Our study provides evidence that inflorescence architecture regulation by SWR1 and ER involves the HBI1 regulatory hub and its activation of both the BR and auxin hormone pathways.

HBI1-TCP20 interaction positively regulates the CEPs-mediated systemic nitrate acquisition.

Nitrate is the main source of nitrogen for plants but often distributed heterogeneously in soil. Plants have evolved sophisticated strategies to achieve adequate nitrate by modulating the root system architecture. The nitrate acquisition system is triggered by the short mobile peptides C-TERMINALLY ENCODED PEPTIDES (CEPs) that are synthesized on the nitrate-starved roots, but induce the expression of nitrate transporters on the other nitrate-rich roots through an unclear signal transduction pathway. Here, we demonstrate that the transcription factors HBI1 and TCP20 play important roles in plant growth and development in response to fluctuating nitrate supply. HBI1 physically interacts with TCP20, and this interaction was enhanced by the nitrate starvation. HBI1 and TCP20 directly bind to the promoters of CEPs and cooperatively induce their expression. Mutation in HBIs and/or TCP20 resulted in impaired systemic nitrate acquisition response. Our solid genetic and molecular evidence strongly indicate that the HBI1-TCP20 module positively regulates the CEPs-mediated systemic nitrate acquisition.

Learning from the past: Impact of the Arctic Oscillation on sea ice and marine productivity off northwest Greenland over the last 9,000 years.

Climate warming is rapidly reshaping the Arctic cryosphere and ocean conditions, with consequences for sea ice and pelagic productivity patterns affecting the entire marine food web. To predict how ongoing changes will impact Arctic marine ecosystems, concerted effort from various disciplines is required. Here, we contribute multi-decadal reconstructions of changes in diatom production and sea-ice conditions in relation to Holocene climate and ocean conditions off northwest Greenland. Our multiproxy study includes diatoms, sea-ice biomarkers (IP25 and HBI III) and geochemical tracers (TOC [total organic carbon], TOC:TN [total nitrogen], δ13 C, δ15 N) from a sediment core record spanning the last c. 9,000 years. Our results suggest that the balance between the outflow of polar water from the Arctic, and input of Atlantic water from the Irminger Current into the West Greenland Current is a key factor in controlling sea-ice conditions, and both diatom phenology and production in northeastern Baffin Bay. Our proxy record notably shows that changes in sea-surface conditions initially forced by Neoglacial cooling were dynamically amplified by the shift in the dominant phase of the Arctic Oscillation (AO) mode that occurred at c. 3,000 yr BP, and caused drastic changes in community composition and a decline in diatom production at the study site. In the future, with projected dominant-positive AO conditions favored by Arctic warming, increased water column stratification may counteract the positive effect of a longer open-water growth season and negatively impact diatom production.

Glucose Homeostasis and the Neonatal Brain: A Sweet Relationship.

Glucose is the primary substrate for energy metabolism in the brain and although the brain is dependent on a constant glucose supply for normal function, both local energy stores and the supply of alternate substrates are limited. In utero, the placenta provides a continuous supply of glucose to the fetus while transition to extrauterine life marks an abrupt change in substrate delivery and a major change in glucose metabolism where insufficiencies and disruptions can occur. Hypoglycemia is one of the most common biochemical disturbances in the neonatal period, affecting a wide range of neonates. Prolonged or persistent low plasma glucose concentrations can lead to neonatal brain injury and abnormal neurological outcomes. This article discusses fetal and neonatal metabolic adaptation, the physiology of glucose homeostasis, hypoglycemic brain injury (HBI), and neurodevelopmental long-term outcomes.

Impaired cognitive function in Crohn's disease: Relationship to disease activity.

BACKGROUND & AIMS: Impaired attention and response inhibition have been reported in patients with Crohn's disease (CD) in clinical remission. Prospective studies are needed to determine whether this is a stable feature of CD and whether a similar impairment is evident in ulcerative colitis (UC). Thus, our aims were to examine whether patients with CD and UC exhibited a persistent impairment in attentional performance, and if this impairment was related to key biological indices of relevance to cognition. METHODS: A prospective observational study was conducted on fifteen patients with CD and 7 with UC in clinical remission recruited from a specialty clinic and 30 healthy matched control participants. A neuropsychological assessment was carried out at baseline (visit 1) and at a 6 month follow-up (visit 2). Plasma proinflammatory cytokines, the plasma kynurenine:tryptophan (Kyn:Trp) ratio and the salivary cortisol awakening response (CAR) were also determined at each visit. RESULTS: Across visits, patients with CD exhibited impaired attentional performance (p â€‹= 0.023). Plasma IL-6 (P â€‹= â€‹0.001) and the Kyn:Trp ratio (P â€‹= â€‹0.03) were consistently elevated and the CAR significantly blunted (P â€‹< â€‹0.05) in patients with CD. No significant relationships were identified between any biochemical parameter and altered cognitive performance. CONCLUSIONS: Impaired cognitive function is a stable feature of patients with CD. These data suggest that even where remission has been achieved, the functional impact of an organic gastrointestinal disorder on cognition is still evident. However, it is unclear at present if physiological changes due to disease activity play a role in cognitive impairment in CD.

HBI1 Mediates the Trade-off between Growth and Immunity through Its Impact on Apoplastic ROS Homeostasis.

Plants continuously need to adapt to their environment and prioritize either growth or defense responses to secure survival and reproduction. Trade-offs between growth and defense are often attributed to the allocation of energy for growth to adaptation responses. Still, the exact mechanisms underlying growth and defense trade-offs are poorly understood. Here, we demonstrate that the growth-related transcription factor HOMOLOG OF BEE2 INTERACTING WITH IBH 1 (HBI1) regulates apoplastic reactive oxygen species (ROS) homeostasis by differentially controlling the expression of NADPH oxidases (NOXs) and peroxidases (POXs). The HBI1 target genes RESPIRATORY BURST OXIDASE HOMOLOG A (RbohA) and RbohC have contrasting effects on the regulation of cell size. In addition, the HBI1-controlled NOXs and POXs oppositely regulate susceptibility toward Pseudomonas syringae. Our findings reveal that the incompatibility between growth and defense programs can be attributed to the way apoplastic ROS homeostasis is modulated during both processes.

Clinical predictors of symptom resolution for children and adolescents with sport-related concussion.

OBJECTIVE: The goal of this study was to determine which variables assessed during an initial clinical evaluation for concussion are independently associated with time until symptom resolution among pediatric patients. METHODS: Data collected from a prospective clinical registry of pediatric patients with concussion were analyzed. The primary outcome variable was time from injury until symptom resolution. Predictor variables assessed within 10 days after injury included preinjury factors, Health and Behavior Inventory scores, headache severity, and balance, vestibular, and oculomotor test performances. The researchers used univariate Cox proportional models to identify potential predictors of symptom resolution time and constructed a multivariate Cox proportional hazards model in which total duration of concussion symptoms remained the outcome variable. RESULTS: The sample consisted of 351 patients (33% female, mean age 14.6 ± 2.2 years, evaluated 5.6 ± 2.6 days after concussion). Univariate Cox proportional hazards models indicated that several variables were associated with a longer duration of symptoms, including headache severity (hazard ratio [HR] 0.90 [95% CI 0.85-0.96]), headache frequency (HR 0.83 [95% CI 0.71-0.96]), confusion (HR 0.79 [95% CI 0.69-0.92]), forgetfulness (HR 0.79 [95% CI 0.68-0.92]), attention difficulties (HR 0.83 [95% CI 0.72-0.96]), trouble remembering (HR 0.84 [95% CI 0.72-0.98]), getting tired often (HR 0.86 [95% CI 0.76-0.97]), getting tired easily (HR 0.86 [95% CI 0.76-0.98]), dizziness (HR 0.86 [95% CI 0.75-0.99]), and abnormal performance on the Romberg test (HR 0.59 [95% CI 0.40-0.85]). A multivariate Cox proportional hazards model indicated that an abnormal performance on the Romberg test was independently associated with a longer duration of symptoms (HR 0.65 [95% CI 0.44-0.98]; p = 0.038). CONCLUSIONS: For children and adolescents evaluated within 10 days after receiving a concussion, abnormal performance on the Romberg test was independently associated with a longer duration of symptoms during recovery. In line with findings of other recent studies investigating predictors of symptom resolution, postural stability tests may provide useful prognostic information for sports medicine clinicians.