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Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce. Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups. Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic. Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI. Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51–13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17–4.36); others vs TNFi: 3.21 (1.59–6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine. Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy. Plain language summary: Changes due to drug failure between biologic therapies: a real-life study in psoriatic arthritis patients Introduction: We wanted to evaluate how often patients with psoriatic arthritis change between different drugs because the drugs weren't working well enough. Additionally, we evaluated which factors could influence the change due to drug failure. The studied drugs are biological therapies that are arthritis-modifying drugs designed early in the last decade to prevent or reduce inflammation caused by the disease. Methods: We included patients from 2007 to 2022 in which their consultant rheumatologist had decided to commence them on biologic therapy. We studied the changes due to drug failure, we also included sociodemographic, clinical and treatments information. Results: The study comprised 141 patients. 52% were women in their fifties. We found that 56 patients change drugs 121 times, with 103 of those changes due to failure drug. This means about 11 out of every 100 patients change their biologic therapy each year. There was no difference in the risk of change between the different studied biologic therapies. Women, those with inflammatory back pain, and those who had tried many different drugs were more likely to change due to drug failure. Using additional therapies like glucocorticoids and sulfasalazine also increased the probability of biologic therapy change. Conclusion: Our work did not find differences in the risk of change due to drug failure among different biologic therapies. [ABSTRACT FROM AUTHOR]

This study aimed to investigate if washing ram sperm from seminal plasma (SP) could be an effective tool to extend sperm lifespan in medium-term preservation in liquid form to optimize ovine artificial insemination protocols. To this end, in Experiment 1 SP was added to a sperm model without previous contact with this substance (ram epididymal sperm) at the beginning or the end of a 48-hour preservation protocol at 5 °C (n = 13). Sperm motility and kinetic parameters and sperm functionality in terms of sperm viability, apoptosis, mitochondrial activity and reacted acrosomes were assessed after 6 h of storage at 15 °C (standard liquid preservation method) and 24 and 48 h at 5 °C. Extended sperm showed better results after 48 h when stored in the absence than in the presence of SP in most sperm quality parameters. Moreover, the final SP supplementation of this experimental group resulted in the highest sperm motility and kinetic parameters, viability and mitochondrial activity. These results suggested that initial SP deprivation could be beneficial in a medium-term ram sperm preservation protocol in liquid form, as well as a final supplementation. Therefore, we conducted Experiment 2 to evaluate the effect of SP removal from freshly ejaculated ram semen under the same storage conditions as in Experiment 1 (n = 12). Surprisingly, SP withdrawal impaired sperm functionality, leading to increased apoptosis and decreased mitochondrial activity after 24 and 48 h at 5 °C. Conversely, SP supplementation at the end of the preservation protocol of the ejaculate processed as usual had a positive effect on sperm quality and fertility. To summarize, SP absence was beneficial for a medium-term preservation protocol (up to 48 h at 5 °C) of ram epididymal sperm, but the same preservation protocol for ram ejaculated sperm revealed a possible failure of the SP removal method in avoiding the sperm-SP interaction effect. Meanwhile, SP supplementation of ram semen at the end of the preservation protocol increased in vitro sperm quality and fertility after artificial insemination. [ABSTRACT FROM AUTHOR]

Aims: Lymph node metastases (LNM) are one of the most important prognostic indicators in solid tumours and a major component of cancer staging. Neoadjuvant therapy might influence nodal status by induction of regression. Our aim is to determine the prevalence and role of regression of LNM on outcomes in patients with rectal cancer. Methods and results: Four independent study populations of rectal cancer patients treated with similar regimens of chemoradiotherapy were pooled together to obtain a total cohort of 469 patients. Post‐treatment nodal status (ypN) and signs of tumour regression (Reg) were incorporated to form three‐tiered (ypN− Reg+, ypN− Reg− and ypN+) and four‐tiered (ypN− Reg+, ypN− Reg−, ypN+ Reg+ and ypN+ Reg−) classifications. In our cohort, 31% of patients presented with ypN+ rectal cancer. As expected, we found significantly worse overall survival (OS) in ypN+ patients compared to ypN− patients (P = 0.002). The percentage of ypN− patients with lymph nodes with complete regression was 20% in our cohort. While node‐negative patients with and without regression had similar OS (P = 0.09), disease‐free survival (DFS) was significantly better in node‐negative patients with regression (P = 0.009). Conclusions: Regression in lymph nodes is frequent, and node‐negative patients with evidence of lymph node regression have better DFS compared to node‐negative patients without such evidence. [ABSTRACT FROM AUTHOR]

Several authors have demonstrated that low levels of reactive oxygen species (ROS) are necessary for the physiological functions of sperm, such as capacitation, hyperactivation, acrosomal reaction and fertilization. However, high levels of ROS are associated with oxidative stress and detrimental effects on fertility. Consequently, deep characterization of ROS presence using different fluorescent probes could be crucial. In this sense, the study of intracellular ROS localization and the relationships between ROS and other conventional parameters could improve the characterization of sperm quality for semen preservation protocols in rams. In this work, a multiparametric study was carried out by analyzing four experimental groups of ram sperm with different initial qualities: fresh semen (from both breeding and nonbreeding seasons), frozen-thawed semen and, a positive control group treated with hydrogen peroxide (300µM) as a marker of extreme damage. Sperm analyses, including viability, apoptosis, lipid peroxidation, motility and kinetic parameters, were applied to compare several experimental groups with different sperm qualities. After that, the signals from two different ROS probes: CellROX™ Deep Red (CRDR) and Green (CRG), were examined by flow cytometry (percentage of cells that express ROS) and fluorescencemicroscopy (intracellular ROS location). Comparing conventional parameters, fresh samples from the breeding season showed the highest sperm quality, while the positive control samples showed the worst sperm quality. Concerning the ROS probes, the CRDR levels were higher in fresh samples from the breeding season than in the positive control and cryopreserved samples. Surprisingly, CRG presented its highest level (P < 0.05) in the positive control group treated with peroxide by flow cytometry. CRDR and CRG presented opposite labeling patterns that were corroborated by fluorescence microscopy, which determined that the probes localized in different parts of sperm. CRDR was found in the sperm mitochondrial region, while CRG was observed in the cell nucleus, suggesting that ROS localization is an important factor. Finally, our study indicates that CRDR is correlated with proper viability and sperm motility, and could be associated with high mitochondrial activity, while CRG is associated with sperm damage. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focused on the importance of accurately assessing ram sperm quality for optimizing assisted reproductive technologies in sheep. Semen preservation can lead to sperm damage due to various stressors, including osmotic, biochemical, and thermal factors. To address this issue, the research aimed to determine the best time to evaluate ram sperm quality and identify the factor causing changes in sperm quality during liquid storage. In Experiment 1, ejaculated sperm were assessed for motility and functionality at different preservation times: 0, 3, 6, and 24 h. Both motility and functionality improved after 6 h. Experiment 2 delved into the responsible factor by using epididymal sperm. Results revealed that extender addition to the sperm caused altered motility at 0 and 24 h, and reduced functionality at 0 h. This suggests that the extender initially alters ram sperm, leading to sublethal damage that becomes reversible after 3 to 6 h of semen preservation. Thus, ram sperm require an adaptation period of 3 to 6 h to the extender before a precise quality assessment. This finding has practical implications for reproduction centers, allowing better workflow organization and optimal expression of ram sperm attributes at the time of cervical artificial insemination. Accurate assessment of ram sperm quality is crucial to optimizing assisted reproductive technologies in sheep. However, semen preservation can induce sperm due to osmotic, biochemical, and thermal stress. Stabilizing sperm with a suitable cooling rate and adaptation period to the extender could mitigate these effects for a more reliable evaluation. This study aimed to determine: (1) the best time to assess ram sperm quality, and (2) the factor responsible for the altered state of ram sperm during the first hours of liquid storage. In Experiment 1, ejaculated sperm were diluted and assessed for sperm motility and functionality at four preservation times: 0, 3, 6, and 24 h as sperm damage control. Both sperm motility and functionality improved after 6 h. Experiment 2 investigated the factor responsible for sperm quality change by testing the interactions of seminal plasma and extender with sperm from epididymides independently and in combination. The evaluation of sperm was performed as in Experiment 1. Sperm in groups containing the extender showed altered motility at 0 and 24 h, and lower functionality at 0 h. Thus, we could assume that extender addition initially alters ram sperm, causing sublethal damage that is reversible after 3 to 6 h of semen preservation. In conclusion, ram sperm require an adaptation time of 3 to 6 h to the extender before an accurate quality assessment can be conducted. This has practical implications for reproduction centers, enabling better workflow organization and optimal expression of ram sperm attributes when cervical artificial insemination is routinely performed. [ABSTRACT FROM AUTHOR]

Background: Alfaxalone is commonly used in veterinary anesthesia for the induction of general anesthesia (GA) in dogs. However, it has been associated with dose-dependent cardiovascular depression. Therefore, the administration of liposoluble, intravenous (IV)-administered injectable induction agents, such as alfaxalone, is recommended to be based on the dog's lean body mass (LBM). Aim: To determine the influence of body condition score (BCS) on IV alfaxalone dose requirements to achieve endotracheal intubation in dogs. Methods: Prospective clinical study. A group of 34 dogs undergoing GA for diagnostic and/or surgical procedures, body weight (BW) > 4 kg, BCS > 2, age 1-14 years, American Society of Anesthesiologists (ASAs) classification I-III. Dogs were allocated to two different groups according to their BCS: non-overweight group (NOW) BCS: 3-5 and over-weight group (OW) BCS: 6-9. All dogs were premedicated IV with methadone 0.2 mg kg-1, and anesthesia was induced by a slow IV infusion of alfaxalone at 1 mg kg-1 minute-1, delivered with a syringe driver, until loss of jaw tone and no/minimal gagging reflex sufficient to allow endotracheal intubation was achieved. The total dose of alfaxalone and the occurrence of post-induction apnoea were recorded. The Shapiro-Wilk test was performed to test for normality. A Chi-square test was performed to compare the incidence of post-induction apnoea between groups, and the Mann-Whitney U test was performed to compare the induction dose of alfaxalone between groups. A p-value < 0.05 was considered statistically significant. Results: The mean dose ± standard deviation of alfaxalone in NOW was 2.18 ± 0.59 mg kg-1, and in OW, it was 1.63 ± 0.26 mg kg-1 (p = 0.002). The sedation score did not differ between groups. Postinduction apnoea (PIA) occurred in 6 of 17 animals in NOW and 15 of 17 in OW (p = 0.002). Conclusion: The dose of IV alfaxalone per kg of total body mass required to achieve endotracheal intubation was lower in overweight dogs, suggesting that LBM should be considered when calculating IV anesthetic doses. The incidence of post-induction apnoea was higher in overweight/obese dogs with alfaxalone administered at a rate of 1 mg kg-1 minute-1. [ABSTRACT FROM AUTHOR]

Aims: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. Methods and results: The study included a test (n = 197) and a validation cohort (n = 218) of post‐CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three‐step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II‐IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19–3.50, P = 0.008) and disease‐free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23–5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. Conclusions: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response. [ABSTRACT FROM AUTHOR]

Simple Summary: Establishing the most suitable tool and the most accurate testicular volume determination formula could be essential in sperm production prediction. Traditionally, the caliper has been used to perform testicular measurements. In recent years, B-mode ultrasound has also been used as a measurement tool, providing, in addition to greater reproducibility as demonstrated in this work, other advantages such as being a non-invasive and non-ionizing technique that allows for the examination of the organ to see pathological processes. In the ovine species, the demand for seminal doses varies according to the genetic value of the donor males. The frequency of semen collection is high in males of great demand and genetic value. Testicular volume has a different influence on sperm production depending on the frequency of semen collection and the season of the year. This study demonstrated the effect of these factors on donor males to improve their reproductive performance. Over the years, testicular volume has been used to evaluate the reproductive capacity of rams and the effects of different factors related to reproductive performance. The aim of this study was to determine the most suitable tool and formula to calculate testicular volume under field conditions to guarantee a more accurate determination of sperm production. First, testicles from 25 rams (n = 50) were measured in vivo and postmortem using calipers and ultrasonography during the breeding season (BS). The accurate testicular volume (ATV) was calculated through water displacement. In addition, the sexual status of donor rams was evaluated during a period of four years in a reproduction center, and the three most crucial groups in terms of genetic value and seminal collections were studied in the second part of this experiment: ER-NBS (Elite rams during the non-breeding season), ER-BS-S (Elite rams with a standard frequency of seminal collection), and ER-BS-O (Elite rams with a high frequency of seminal collection). The total testicular volume (TTV), testosterone (T), and total spermatozoa obtained from two consecutive ejaculates in the same day (SPERM) were measured, and the relationship between SPERM and TTV and T was analyzed to predict SPERM. Although all published formulas revealed statistically significant differences (p ≤ 0.05) from the ATV, our proposed formula (ItraULE) (Testicular volume = L × W × D × 0.61) did not show significant differences. In the second part of the study, in the ER as a model donor ram for its high genetic value and high demand from farmers, TTV and T showed strong positive correlations with SPERM (r = 0.587, p = 0.007 NBS; r = 0.684, p = 0.001 BS-S; r = 0.773, p < 0.0001 BS-O). Moreover, formulas were established to predict SPERM in these practical scenarios. In conclusion, the use of ultrasonography and a new formula adapted to rams could improve the prediction of SPERM considering crucial factors such as season and semen collection frequency. [ABSTRACT FROM AUTHOR]

Background: Amblyopia is the most common developmental vision disorder in children. The initial treatment consists of refractive correction. When insufficient, occlusion therapy may further improve visual acuity. However, the challenges and compliance issues associated with occlusion therapy may result in treatment failure and residual amblyopia. Virtual reality (VR) games developed to improve visual function have shown positive preliminary results. The aim of this study is to determine the efficacy of these games to improve vision, attention, and motor skills in patients with residual amblyopia and identify brain-related changes. We hypothesize that a VR-based training with the suggested ingredients (3D cues and rich feedback), combined with increasing the difficulty level and the use of various games in a home-based environment is crucial for treatment efficacy of vision recovery, and may be particularly effective in children. Methods: The AMBER study is a randomized, cross-over, controlled trial designed to assess the effect of binocular stimulation (VR-based stereoptic serious games) in individuals with residual amblyopia (n = 30, 6–35 years of age), compared to refractive correction on vision, selective attention and motor control skills. Additionally, they will be compared to a control group of age-matched healthy individuals (n = 30) to account for the unique benefit of VR-based serious games. All participants will play serious games 30 min per day, 5 days per week, for 8 weeks. The games are delivered with the Vivid Vision Home software. The amblyopic cohort will receive both treatments in a randomized order according to the type of amblyopia, while the control group will only receive the VR-based stereoscopic serious games. The primary outcome is visual acuity in the amblyopic eye. Secondary outcomes include stereoacuity, functional vision, cortical visual responses, selective attention, and motor control. The outcomes will be measured before and after each treatment with 8-week follow-up. Discussion: The VR-based games used in this study have been conceived to deliver binocular visual stimulation tailored to the individual visual needs of the patient, which will potentially result in improved basic and functional vision skills as well as visual attention and motor control skills. Trial registration: This protocol is registered on ClinicalTrials.gov (identifier: NCT05114252) and in the Swiss National Clinical Trials Portal (identifier: SNCTP000005024). [ABSTRACT FROM AUTHOR]

Simple Summary: The use of combined estrus synchronization/superovulation (SS) treatments alters ovarian and endometrial gene expression patterns, impairing follicle and oocyte growth, fertilization, and embryo development. Since the impact of SS treatments on the transcriptome of the surviving embryos remains unidentified, we examined gene expression changes in day 6 blastocysts that survived a brief regimen of synchronization treatment combined with superovulation. Embryos were surgically collected on day 6 after AI, and transcriptome analysis was performed on blastocyst-stage embryos with good morphology to identify differentially expressed genes (DEGs) between groups at p-value < 0.05 and 1.5-fold change. Compared with the blastocysts from control (untreated) sows, the blastocysts from SS-treated sows had moderate gene expression changes, with 7 pathways disrupted and a total of 10 transcripts affected, including up-regulation of metabolic RDH10 and SPTLC2 genes and down-regulation of oxidation-related GSTK1 and GSTO1 genes. These gene expression alterations may suggest suboptimal embryo quality and could depress the embryos' response to oxidative stress, thereby impairing subsequent embryo development. These and previous findings call for the avoidance of SS treatments in embryo transfer programs. The combination of estrus synchronization and superovulation (SS) treatments causes alterations in ovarian and endometrial gene expression patterns, resulting in abnormal follicle and oocyte growth, fertilization, and embryo development. However, the impact of combined SS treatments on the transcriptome of the surviving embryos remains unidentified. In this study, we examined gene expression changes in day 6 blastocysts that survived a brief regimen of synchronization treatment combined with superovulation. The sows were included in one of three groups: SS7 group (n = 6), sows were administered Altrenogest (ALT) 7 days from the day of weaning and superovulated with eCG 24 h after the end of ALT treatment and hCG at the onset of estrus; SO group (n = 6), ALT nontreated sows were superovulated with eCG 24 h postweaning and hCG at the onset of estrus; control group (n = 6), weaned sows displaying natural estrus. Six days after insemination, the sows underwent a surgical intervention for embryo collection. Transcriptome analysis was performed on blastocyst-stage embryos with good morphology. Differentially expressed genes (DEGs) between groups were detected using one-way ANOVA with an un-adjusted p-value < 0.05 and a fold change 1.5. The effect of SO treatment on the number of altered pathways and DEGs within each pathway was minimal. Only four pathways were disrupted comprising only a total of four altered transcripts, which were not related to reproductive functions or embryonic development. On the other hand, the surviving blastocysts subjected to SS7 treatments exhibited moderate gene expression changes in terms of DEGs and fold changes, with seven pathways disrupted containing a total of 10 transcripts affected. In this case, the up-regulation of certain pathways, such as the metabolic pathway, with two up-regulated genes associated with reproductive functions, namely RDH10 and SPTLC2, may suggest suboptimal embryo quality, while the down-regulation of others, such as the glutathione metabolism pathway, with down-regulated genes related to cellular detoxification of reactive oxygen species, namely GSTK1 and GSTO1, could depress the embryos' response to oxidative stress, thereby impairing subsequent embryo development. The gene expression changes observed in the present study in SS7 embryos, along with previous reports indicating SS7 can negatively affect fertilization, embryo production, and reproductive tract gene expression, make its use in embryo transfer programs unrecommendable. [ABSTRACT FROM AUTHOR]

We explored structural brain connectomes in children with spastic unilateral cerebral palsy (uCP) and its relation to sensory‐motor function using graph theory. In 46 children with uCP (mean age = 10 years 7 months ± 2 years 9 months; Manual Ability Classification System I = 15, II = 16, III = 15) we assessed upper limb somatosensory and motor function. We collected multi‐shell diffusion‐weighted, T1‐weighted and T2‐FLAIR MRI and identified the corticospinal tract (CST) wiring pattern using transcranial magnetic stimulation. Structural connectomes were constructed using Virtual Brain Grafting‐modified FreeSurfer parcellations and multi‐shell multi‐tissue constrained spherical deconvolution‐based anatomically‐constrained tractography. Graph metrics (characteristic path length, global/local efficiency and clustering coefficient) of the whole brain, the ipsilesional/contralesional hemisphere, and the full/ipsilesional/contralesional sensory‐motor network were compared between lesion types (periventricular white matter (PWM) = 28, cortical and deep gray matter (CDGM) = 18) and CST‐wiring patterns (ipsilateral = 14, bilateral = 14, contralateral = 12, unknown = 6) using ANCOVA with age as covariate. Using elastic‐net regularized regression we investigated how graph metrics, lesion volume, lesion type, CST‐wiring pattern and age predicted sensory‐motor function. In both the whole brain and subnetworks, we observed a hyperconnectivity pattern in children with CDGM‐lesions compared with PWM‐lesions, with higher clustering coefficient (p = [<.001–.047], ηp2=[0.09–0.27]), characteristic path length (p =.003, ηp2=0.19) and local efficiency (p = [.001–.02], ηp2=[0.11–0.21]), and a lower global efficiency with age (p = [.01–.04], ηp2=[0.09–0.15]). No differences were found between CST‐wiring groups. Overall, good predictions of sensory‐motor function were obtained with elastic‐net regression (R2 =.40–.87). CST‐wiring pattern was the strongest predictor for motor function. For somatosensory function, all independent variables contributed equally to the model. In conclusion, we demonstrated the potential of structural connectomics in understanding disease severity and brain development in children with uCP. [ABSTRACT FROM AUTHOR]

In recent years, there has been a rapid proliferation of novel tobacco and nicotine products in the market, which have gained in popularity among adolescents. The prevalence of ever users of electronic cigarettes (e-cigs) in Europe among those aged 10–24 ranges from 5.5% to 56.6%, with significant variations across countries. Adolescents have reported several reasons for e-cig use initiation, including low harm perception, social acceptability, novelty, and peer influence. Despite being marketed as safe alternatives, e-cigs are not risk-free and have already been associated with respiratory diseases. A major concern is their potential to renormalize smoking among non-smokers and to foster nicotine dependence, leading to the initiation of conventional cigarette smoking, which would reverse actual declining trends in tobacco consumption. Hence, to prevent a setback on the progress made in tobacco control, there is a pressing need for more comprehensive regulation, with a particular focus on adolescents, given that the teenage years are pivotal in determining future smoking behavior. [ABSTRACT FROM AUTHOR]

Aim: To design and implement a plan to improve oncohaematological patients' sleep. Background: The hospital environment can compromise inpatients' sleep, negatively impacting on health outcomes and patient satisfaction. Design and Method: The improvement plan was designed in collaboration with 18 professionals, 3 patients and 3 accompanying relatives. The study designed followed the SQUIRE 2.0 guidelines. Outcome variables were self‐reported patient satisfaction regarding sleep, measured using a 30‐item, ad hoc questionnaire and a 10‐point visual analogue scale, completed by 318 oncohaematological inpatients (pre‐intervention n = 120, post‐intervention, n = 198) in a comprehensive cancer centre in Spain from 2017 to 2019. Results: Overall, 61.5% (n = 190) of the inpatients reported sleep alterations, and 92.6% reported interruptions in their nightly sleep. Half slept less than 6 h/night, but 58.0% said they felt rested upon waking, despite the interruptions. These outcomes were similar before and after the intervention. The improvement plan identified four domains for work (professionals, care procedures, instruments/environment and patients/relatives), 10 areas for improvement and 35 actions for implementation. However, overall sleep worsened significantly, from 6.73 to 6.06 on the 10‐point scale. The intervention significantly improved variables related to professionals' behaviour, including noise during the shift change, conversations at the control desk and the use of corridor lights. Sleep disturbances were mainly caused by pain/discomfort and infuser alarms, and collectively they decreased significantly after the intervention (p =.008). However, overall sleep worsened significantly, from 6.73 to 6.06 on the 10‐point scale. Conclusions: Pain, clinical devices and noise made by professionals are the main causes of sleep disturbances. Involving professionals in decision‐making to improve patients' sleep have a positive impact on noise levels. Relevance to clinical practice: This study proposes new strategies for improving sleep by increasing staff awareness and changing attitudes towards patients' sleep. Nurses should be involved in addressing sleep disturbances during hospitalization. [ABSTRACT FROM AUTHOR]

Objective: Test a culturally tailored obesity prevention intervention in low-income, minority preschool-age children.Design: A three-group clustered randomized controlled trial.Setting: Twelve Head Start Centers were randomly assigned to a center-based intervention, a combined center- and home-based intervention, or control using a 1:1:1 ratio. The center-based intervention modified center physical activity and nutrition policies, staff practices, and child behaviors, while the home-based intervention supported parents for obesity prevention at home.Study Outcomes: The primary endpoint was change in children's body mass index (BMI; kg/m2) at posttest immediately following completion of the 8-month intervention. Secondary endpoints included standardized scores for BMI (BMIz) and body weight (WAZ), and BMI percentiles (BMI pctl).Participants: Three-year-old children enrolled in Head Start in San Antonio, Texas, with written parent consent (N=325), 87% Latino; 57% female with mean age (SD) of 3.58 years (0.29).Results: Change in BMI at posttest was 1.28 (0.97), 1.28 (0.87), and 1.41 (0.71) in the center+home-based intervention, center-based intervention, and control, respectively. There was no significant difference in BMI change between center+home-based intervention and control or center-based intervention and control at posttest. BMIz (adjusted difference -0.12 [95% CI, -0.24 to 0.01], p = .06) and WAZ (adjusted difference, -0.09 [-0.17 to -0.002], p = .04) were reduced for children in center+home-based intervention compared to control group.Conclusions: There was no reduction in BMI at posttest in children who received the intervention. Findings shed light on methodological challenges in childhood obesity research and offer future directions to explore health equity-oriented obesity prevention. [ABSTRACT FROM AUTHOR]

Not only do soils provide 98.7% of the calories consumed by humans, they also provide numerous other functions upon which planetary survivability closely depends. However, our continuously increasing focus on soils for biomass provision (food, fiber, and energy) through intensive agriculture is rapidly degrading soils and diminishing their capacity to deliver other vital functions. These tradeoffs in soil functionality – the increased provision of one function at the expense of other critical planetary functions – are the focus of this review. We examine how land-use change for biomass provision has decreased the ability of soils to regulate the carbon pool and thereby contribute profoundly to climate change, to cycle the nutrients that sustain plant growth and ecosystem health, to protect the soil biodiversity upon which many other functions depend, and to cycle the Earth's freshwater supplies. We also examine how this decreasing ability of soil to provide these other functions can be halted and reversed. Despite the complexity and the interconnectedness of soil functions, we show that soil organic carbon plays a central role and is a master indicator for soil functioning and that we require a better understanding of the factors controlling the behavior and persistence of C in soils. Given the threats facing humanity and their economies, it is imperative that we recognize that Soil Security is itself an existential challenge and that we need to increase our focus on the multiple functions of soils for long-term human welfare and survivability of the planet. [ABSTRACT FROM AUTHOR]

Type 6 secretion systems (T6SSs) are specialized multiprotein complexes that inject protein effectors into prokaryotic and/or eukaryotic cells. We previously described the role of the T6SS of the phytopathogen Xanthomonas citri pv. citri as an anti‐eukaryotic nanoweapon that confers resistance to predation by the amoeba Dictyostelium discoideum. Transcription of the X. citri T6SS genes is induced by a signaling cascade involving the Ser/Thr kinase PknS and the extracytoplasmic function sigma factor EcfK. Here, we used a strain overexpressing a phosphomimetic constitutively active version of EcfK (EcfKT51E) to identify the EcfK regulon, which includes a previously uncharacterized transcription factor of the AraC‐family (TagK), in addition to T6SS genes and genes encoding protein homeostasis factors. Functional studies demonstrated that TagK acts downstream of EcfK, binding directly to T6SS gene promoters and inducing T6SS expression in response to contact with amoeba cells. TagK controls a small regulon, consisting of the complete T6SS, its accessory genes and additional genes encoded within the T6SS cluster. We conclude that a singular regulatory circuit consisting of a transmembrane kinase (PknS), an alternative sigma factor (EcfK) and an AraC‐type transcriptional regulator (TagK) promotes expression of the X. citri T6SS in response to a protozoan predator. [ABSTRACT FROM AUTHOR]

The combination of estrus synchronization and superovulation treatments introduces molecular modifications whose effects are yet to be disclosed. Here, reproductive parameters and gene expression changes in ovaries and endometrium were explored on day 6 after artificial insemination (AI), when synthetic progestin altrenogest (ALT) was combined with gonadotropins. Sows were administered ALT for 7 d beginning on the day of weaning and superovulated with equine chorionic gonadotropin (eCG) 24 h later and human chorionic gonadotropins (hCG) at the onset of estrus (SS-7 group; n = 6). The controls were either superovulated sows with eCG 24 h postweaning and hCG at the onset of estrus (SC group; n = 6) or sows with postweaning spontaneous estrus (NC group; n = 6). Ovary examination and embryo and tissue collection were performed in all sows via laparotomy on day 6 post-AI. RNA-Seq was conducted to analyze differentially expressed genes (DEGs) between groups. Statistical analysis of the reproductive parameters was conducted with ANOVA and Tukey post hoc tests. DEGs were analyzed with an ANOVA (fold changes ≥2 or ≤2, P value <0.05). Hormonal treatments almost doubled (P < 0.03) the number of corpora lutea (39.8 ± 10.2 and 38.3 ± 11.1 in SS-7 and SC sows, respectively) compared with that in the NC group (23.1 ± 3.8). In contrast, embryo viability significantly decreased (P < 0.003) in response to SS-7 treatment (75.1% ± 15.2%) compared to SC and NC groups (93.8 ± 7.6% and 91.8 ± 6.9%, respectively). RNA-Seq analyses revealed 675 and 1,583 DEGs in the SS-7 group compared to both SC and NC groups in endometrial and ovarian samples, respectively. Interestingly, many genes with key roles in the Wnt/β-catenin and Notch signaling pathways were differentially expressed in SS-7 sows relative to SC and NC groups (e.g., Ctnnb1, Myc, Gli3, Scyl2, Ccny, Daam1, Ppm1n, Rbpj, and Usp8). A key finding in this study was the downregulation of β-catenin (Ctnnb1) gene expression in the SS-7 endometrium, suggesting that this treatment influences embryo–uterine dialogue by triggering a cascade of events leading to embryo maldevelopment. These data explain the proliferative defects in SS-7 embryos and suggest a novel mechanism of a porcine embryo–maternal crosstalk. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate the effects of different equilibration times with cryoprotectants on viability and metaphase plate morphology of vitrified‐warmed porcine mature oocytes (Experiment 1) and to evaluate the effects of supplementation with 10−9 M melatonin during in vitro maturation on these parameters (Experiment 2). In Experiment 1, 2,392 mature oocytes were vitrified using different equilibration times of oocytes with cryoprotectants (3, 10, 15, 20, 30, 40, 60 and 80 min). Fresh oocytes matured in vitro for 44 hr (n = 509) were used as controls. In Experiment 2, a total of 573 COCs were used. COCs were matured with 10−9 M melatonin supplementation or without melatonin (control). Some oocytes from each group were vitrified with a 60‐min equilibration time with cryoprotectants according to the results of Experiment 1. The remaining oocytes from each maturation group were used as fresh control groups. In both experiments, oocytes were stained with 2′,7′‐dichlorodihydrofuorescein diacetate and Hoechst 33342 to assess viability and metaphase plate morphology, respectively. Vitrification and warming affected (p <.01) oocyte viability compared with controls, which were all viable after 44 hr of IVM. In Experiment 1, the longer the equilibration time with cryoprotectants, the higher the viability. Oocytes equilibrated for 60 and 80 min had the highest (p <.05) viability and similar metaphase plate characteristics to the fresh control oocytes. In Experiment 2, supplementation with melatonin during in vitro maturation had no effect on oocyte viability or metaphase plate morphology of vitrified‐warmed oocytes. In conclusion, under our experimental conditions, vitrified porcine mature oocytes equilibrated with cryoprotectants for 60 or 80 min exhibited the highest viability and similar metaphase plate characteristics to fresh controls. Furthermore, supplementation with 10−9 M melatonin during in vitro maturation had no effect on these parameters. [ABSTRACT FROM AUTHOR]

Artificial insemination (AI) for pigs relies on liquid storage of extended semen at 17°C, which preserves sperm quality and ensures its fertilizing capacity. Routine quality controls include the evaluation of sperm motility, viability and capacitation status. The physiological functions of all these features depend on transmembrane aquaporins (AQPs), proteins playing key roles in osmoadaptation. In this study, we made a relative quantification, using RT‐qPCR, of the mRNA of several sperm AQPs in AI‐liquid semen doses before and after a 48‐hr incubation period, aiming to determine possible quantitative compromising expression changes during the process that could serve as a diagnostic tool. Our results showed a decrease in classical sperm motility variables (total and progressive motility and velocity) and sperm viability after 48‐hr storage, whereas capacitation status increased overtime. mRNA expression increased in the orthodox AQP4 and AQP6 after 48‐hr incubation, relative to control (0 hr) and 24‐hr time‐points. Moreover, mRNA expression of aquaglyceroporins AQP3, AQP7 and AQP10 was higher after 48‐hr incubation, confirmed by AQP7‐protein validation using Western blot. Our results indicate that expression levels of AQPs‐mRNA can change in ejaculated pig spermatozoa under conditions of ex‐vivo incubation that could modify sperm homeostasis, suggesting it could eventually become a relevant molecular biomarker to assess the efficiency of liquid storage of pig semen. [ABSTRACT FROM AUTHOR]

Aim: We explored the psychometric properties of the recently developed Tyneside Pegboard Test (TPT) for unimanual and bimanual dexterity in children with unilateral cerebral palsy (CP) and investigated the impact of sensorimotor impairments on manual dexterity.Method: In this cross-sectional study, the TPT was assessed in 49 children with unilateral CP (mean age 9y 8mo, SD 1y 11mo, range 6-15y; 30 males, 19 females; 23 with right unilateral CP). All participants additionally underwent a standardized upper limb evaluation at body function and activity level. We investigated: (1) known-group, concurrent, and construct validity and (2) impact of sensorimotor impairments including spasticity, grip force, stereognosis, and mirror movements using analysis of covariance, Spearman's rank correlation (r), and multiple linear regression (R2 ) respectively.Results: TPT outcomes significantly differed according to the Manual Ability Classification System (p<0.001, known-group validity). Relationships were found between the unimanual TPT tasks and the Jebsen-Taylor Hand Function Test (r=0.86-0.88, concurrent validity). Bimanual TPT tasks were negatively correlated with the Assisting Hand Assessment, ABILHAND-Kids, and Children's Hand-use Experience Questionnaire (r=-0.38 to -0.78, construct validity). Stereognosis was the main determinant influencing all tasks (p<0.001, R2 =37-50%). Unimanual dexterity was additionally determined by grip strength (p<0.05, R2 =8-9%) and mirror movements in the more impaired hand (p<0.05, R2 =4-8%). Bimanual dexterity was also explained by mirror movements in the more impaired hand (p<0.01, R2 =10-16%) and spasticity (p=0.04, R2 =5%).Interpretation: The TPT is a valid test to measure unimanual and bimanual dexterity in unilateral CP. The results further emphasize the importance of somatosensory impairments in children with unilateral CP. What this paper adds The Tyneside Pegboard Test is valid for measuring unimanual and bimanual dexterity in unilateral cerebral palsy. Children with poorer manual ability show worse unimanual and bimanual dexterity. Stereognosis is the main predictor of both unimanual and bimanual dexterity. Stronger mirror movements in the more impaired hand result in worse bimanual dexterity. [ABSTRACT FROM AUTHOR]

Mirror movements (MM) influence bimanual performance in children with unilateral cerebral palsy (uCP). Whilst MM are related to brain lesion characteristics and the corticospinal tract (CST) wiring pattern, the combined impact of these neurological factors remains unknown. Forty-nine children with uCP (mean age 10y6mo) performed a repetitive squeezing task to quantify similarity (MM-similarity) and strength (MM-intensity) of the MM activity. We used MRI data to evaluate lesion type (periventricular white matter, N = 30; cortico-subcortical, N = 19), extent of ipsilesional damage, presence of bilateral lesions, and damage to basal ganglia, thalamus and corpus callosum. The CST wiring was assessed with Transcranial Magnetic Stimulation (17 CSTcontralateral, 16 CSTipsilateral, 16 CSTbilateral). Data was analyzed with regression analyses. In the more-affected hand, MM-similarity and intensity were higher with CSTbilateral/ipsilateral. In the less-affected hand, MM-similarity was higher in children with (1) CSTcontra with CSC lesions, (2) CSTbilat/ipsi with PVL lesions and (3) CSTbilat/ipsi with unilateralized lesions. MM-intensity was higher with larger damage to the corpus callosum and unilateral lesions. A complex combination of neurological factors influences MM characteristics, and the mechanisms differ between hands. [ABSTRACT FROM AUTHOR]

Aim: Currently, compelling evidence illustrates the significance of determining microsatellite instability (MSI) in colorectal cancer (CRC). The association of MSI with proximal CRC is well established, however, its implications in patients with rectal cancer remain undefined. We therefore aimed to determine the role of MSI with respect to incidence and outcome in patients with rectal cancer. Methods and Results: For this we examined patients from two prospective phase III trials: TME trial and PROCTOR‐SCRIPT trial (n = 1250). In addition, we performed a literature review to evaluate the overall prevalence, the effect on survival and the response to neo‐adjuvant treatment in patients with MSI rectal cancer compared with microsatellite stable (MSS) rectal cancer. Our TME and PROCTOR‐SCRIPT cohort showed no differences in terms of overall survival (OS) (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.69–1.47) and disease‐free survival (DFS) (HR 1.00, 95% CI 0.68–1.45) in patients with MSI compared to MSS rectal cancer. The total number of MSI cases in all included studies (including our own) was 1220 (out of 16,526 rectal cancer patients), with an overall prevalence of 6.7% (standard error 1.19%). Both for OS as for DFS there was no impact of MSI status on prognosis (HR 1.00, 95% CI 0.77–1.29 and HR 0.86, 95% CI 0.60–1.22, respectively). The risk ratio (RR) for downstaging and pathological complete response showed also no impact of MSI status (RR 1.15, 95% CI 0.86–1.55 and RR 0.81, 95% CI 0.54–1.22, respectively). Conclusion: Rectal cancer patients with MSI form a distinct and rare subcategory, however, there is no prognostic effect of MSI in rectal cancer patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the inter- and intrarater reliability of the Woods and Teuber scale to detect mirror movements in children and adolescents with unilateral cerebral palsy (CP).Method: A convenience sample of children and adolescents with unilateral CP (n=68; 31 males, 37 females; mean age 12y 2mo, SD 3y 6mo) in Manual Ability Classification levels I to III was recruited from Norway, Australia, and Belgium. Three therapists scored mirror movements according to the Woods and Teuber scale from three video-recorded tasks at two separate time points. A two-way, mixed model regression was used to calculate intraclass correlation coefficients (ICCs) reflecting overall inter- and intrarater reliability. In addition, ICCs for each hand and task were calculated separately.Results: The overall interrater reliability ICC was 0.90 and the corresponding intrarater reliability ICC was 0.92. The ICCs for each hand ranged from 0.86 to 0.92 and for each task from 0.63 to 0.89.Interpretation: The Woods and Teuber scale shows excellent reliability for scoring mirror movements in children and adolescents with unilateral CP. The assessment is easy to administer with no need for specific equipment and scoring can be determined from short video recordings, making it a feasible instrument in research and clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Sperm cryopreservation is an important step to optimize artificial insemination protocols for rams. Traditionally, the improvement of ram sperm cryopreservation protocols has been addressed through different methods: formulation of different cryoprotectants, supplementation with antioxidants or carrying out different freezing-thawing rates. However, the influence of the male sexual regime as a factor for the improvement of freezability has not been studied until now. The frequency of sperm collection in the work protocols of reproduction centers can be variable depending on the dose demand. To corroborate the variability of the quality of thawed semen according to the frequency of collection, in addition to traditional analyses, new tests based on the redox balance of spermatozoa were performed. All these aspects have been applied and discussed extensively throughout this manuscript. In addition, new approaches, such as antioxidant activity of some enzymes have been incorporated to provide more precision in integrative studies of the redox state in spermatozoa. The deleterious effect triggered by a high dose demand should be demonstrated as a consequence of a redox imbalance. The improvement of frozen-thawed sperm quality has been mostly approached from the view of cryopreservation protocol optimization in terms of cryoprotectant solutions, freezing-thawing rates and antioxidant supplementation, while the impact of sperm collection frequency remains unknown in rams. In this work, a multiparametric study was carried out in cooled and frozen-thawed semen to evaluate sperm quality after different semen collection frequencies during a month: zero sperm collection (0 CW), four sperm collections per week (4 CW), and ten sperm collections per week (10 CW). Traditional analyses have been applied, in combination with novel technologies related to redox balance. Frozen-thawed semen quality showed a significant decrease (p < 0.05) in 0 CW and 10 CW in comparison to 4 CW, concerning motility and kinetics parameters. However, apoptosis showed a significant increase (p < 0.05) in 10 CW in comparison to 0 CW and 4 CW. The employment methods related to redox balance provided us with the definitive probe to ensure the influence of collection frequency on balance redox after thawing. Specifically, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity showed a significant decrease (p < 0.05) in 10 CW compared to 0 CW and 4 CW. The characterization of alternative strategies to sperm cryopreservation based on consideration of male sexual regimes, could improve the quality of frozen-thawed sperm. [ABSTRACT FROM AUTHOR]

Cloned and transgenic pigs are relevant human disease models and serve as potential donors for regenerative medicine and xenotransplantation. These technologies demand oocytes and embryos of good quality. However, the current protocols for in vitro production (IVP) of pig embryos give reduced blastocyst efficiency and embryo quality compared to in vivo controls. This is likely due to culture conditions jeopardizing embryonic homeostasis including the effect of reactive oxygen species (ROS) influence. In this study, the antioxidant melatonin (1 nM) in the maturation medium, fertilization medium, or both media was ineffective in enhancing fertilization or embryonic development parameters of in vitro fertilized oocytes. Supplementation of melatonin in the fertilization medium also had no effect on sperm function. In contrast, the addition of melatonin to the embryo culture medium accelerated the timing of embryonic development and increased the percentages of cleaved embryos and presumed zygotes that developed to the blastocyst stage. Furthermore, it increased the number of inner mass cells and the inner mass cell/total cell number ratio per blastocyst while increasing intracellular glutathione and reducing ROS and DNA damage levels in embryos. Contrarily, the addition of melatonin to the embryo culture medium had no evident effect on in vivo-derived embryos, including the developmental capacity and the quality of in vivo-derived 4-cell embryos or the percentage of genome-edited in vivo-derived zygotes achieving the blastocyst stage. In conclusion, exogenous melatonin in the embryo culture medium enhances the development and quality of in vitro-derived embryos but not in in vivo-derived embryos. Exogenous melatonin is thus recommended during embryo culture of oocytes matured and fertilized in vitro for improving porcine IVP efficiency. [ABSTRACT FROM AUTHOR]

Eosinophils are innate immune granulocytes actively involved in defensive responses and in local and systemic inflammatory processes. Beyond these effector roles, eosinophils are fundamental to maintaining homeostasis in the tissues they reside. Gastrointestinal eosinophils modulate barrier function and mucosal immunity and promote tissue development through their direct communication with almost every cellular component. This is possible thanks to the variety of receptors they express and the bioactive molecules they store and release, including cytotoxic proteins, cytokines, growth factors, and neuropeptides and neurotrophines. A growing body of evidence points to the eosinophil as a key neuro-immune player in the regulation of gastrointestinal function, with potential implications in pathophysiological processes. Eosinophil–neuron interactions are facilitated by chemotaxis and adhesion molecules, and the mediators released may have excitatory or inhibitory effects on each cell type, with physiological consequences dependent on the type of innervation involved. Of special interest are the disorders of the brain–gut interaction (DBGIs), mainly functional dyspepsia (FD) and irritable bowel syndrome (IBS), in which mucosal eosinophilia and eosinophil activation have been identified. In this review, we summarize the main roles of gastrointestinal eosinophils in supporting gut homeostasis and the evidence available on eosinophil–neuron interactions to bring new insights that support the fundamental role of this neuro-immune crosstalk in maintaining gut health and contributing to the pathophysiology of DBGIs. [ABSTRACT FROM AUTHOR]

Aims: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival. Methods and results: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper‐gastrointestinal (GI) centres (2005–18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre‐defined three‐step flowchart. The results were validated in an external cohort (2001–17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5–5.6] and poorer 5‐year overall survival (30 versus 80% respectively, P = 0.001). Conclusions: The validation cohort confirmed these findings, although had more advanced cases (case‐stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented‐pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0–3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response. [ABSTRACT FROM AUTHOR]

Background Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. Methods The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. Results The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. Conclusions We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients. [ABSTRACT FROM AUTHOR]

The "2 SP nd sp Workshop in Microbial Molecular Biology" was the second edition of a scientific meeting organized by the molecular microbiology community of São Paulo State (Brazil) and was held over 3 days (5-7 December), at the University of Campinas (UNICAMP), Campinas, Brazil. Next, Marco Vinolo (Institute of Biology/UNICAMP) showed us how metabolites from the host microbiota modulate the immune response to bacterial and virus pathogens. The student Enzo Sichi de Mello presented results obtained during his ongoing undergraduate internship at Cristina Alvarez-Martinez laboratory (Institute of Biology, UNICAMP) about the signaling pathway that induces an anti-amoeba T6SS of I X. citri i . [Extracted from the article]

Background Activation of parietal–epithelial cells (PECs) with neo-expression of CD44 has been found to play a relevant role in the development of focal and segmental glomerulosclerosis (FSGS). The aim of this study was to analyse whether the expression of CD44 by PECs in biopsies of minimal change disease (MCD) is associated with the response to corticosteroids, with kidney outcomes and/or can be considered an early sign of FSGS. Methods This multicentric, retrospective study included paediatric and adult patients with MCD. Demographic, clinical and biochemical data were recorded, and biopsies were stained with anti-CD44 antibodies. The association between PECs, CD44 expression and the response to corticosteroids, and kidney outcomes were analysed using logistic, Kaplan–Meier and Cox regression analyses. Results A total of 54 patients were included: 35 (65%) <18 years and 19 (35%) adults. Mean follow-up was 68.3 ± 37.9 months. A total of 19/54 patients (35.2%) showed CD44-positive staining. CD44-positive patients were younger (14.5 ± 5 versus 21.5 ± 13, P = 0.006), and showed a higher incidence of steroid-resistance [11/19 (57.8%) versus 7/35 (20%), P = 0.021; odds ratio: 5.5 (95% confidence interval 1.6–18), P = 0.007] and chronic kidney disease [9/19 (47.3%) versus 6/35 (17.1%), P = 0.021; relative risk: 3.01 (95% confidence interval 1.07–8.5), P = 0.037]. Follow-up re-biopsies of native kidneys (n = 18), identified FSGS lesions in 10/12 (83.3%) of first-biopsy CD44-positive patients versus 1/6 (16.7%) of first-biopsy CD44-negative patients (P = 0.026). Conclusions In patients with a light microscopy pattern of MCD, CD44-positive staining of PECs is associated with a higher prevalence of steroid resistance and worse kidney outcomes, and can be considered an early sign of FSGS. [ABSTRACT FROM AUTHOR]

The 15 N natural abundance (NA) method is increasingly used to quantify fertiliser N recovery by crops, even though this method does not always provide comparable results to those obtained using 15 N-enrichment (EN). This study assessed the ability of both methods to quantify urea-N recovery by maize (Zea mays) in soils with different management histories. A pot experiment was conducted using eight soils that differed in tillage, stubble management, and N fertiliser use history. Urea-N (unlabelled or 15 N-enriched at 10 atom-%) was applied at a rate equivalent to 150 kg N ha−1 prior to sowing maize. Method comparison was based on N recovery efficiency (REN) and N derived from fertiliser (Ndff). Maize grown in soils without fertiliser N history had significantly higher δ15N and Ndff but lower REN, than soils with fertiliser N histories. The NA method also consistently estimated 10% lower REN and Ndff than the EN method regardless of management history, although fertiliser N history affected the relationship between the methods. A highly significant linear relationship was obtained for REN measured using NA and EN methods (R2 = 0.98) in soils without fertiliser N history, but no relationship was apparent for soils with a long fertiliser N history. In conclusion, (1) the significant effect of fertiliser N history on the isotopic signature of soil N will limit the use of the NA method if soils with different N fertiliser histories are studied; and (2) REN and Ndff determined by NA were consistently lower than the EN method. [ABSTRACT FROM AUTHOR]

Enhanced efficiency nitrogen fertilisers (EENFs) attempt to improve nitrogen use efficiency (NUE) by synchronizing nitrogen (N) supply with crop demand to improve crop productivity/profitability and minimize environmental impacts. This study evaluated the impact of ten EENFs (at 125 and 250 kg N ha−1) compared to urea-N (at 0, 62.5, 125, 175, 250 and 300 kg N ha−1) subsurface banded in a no-till maize (Zea mays L.) production system. Crop growth was examined in both the year of application and in the following year (without fertiliser N) to assess residual impacts. Nitrous oxide emissions from a subset of EENFs applied at 150 kg N ha−1 in an adjacent experiment were monitored in year 1. Grain yield increased with increasing rates of applied urea-N in year 1, with a maximum potential yield of 11.2 t ha−1 achieved at ≥ 175 kg N ha−1. However, grain and biomass yield, agronomic NUE, and N transfer efficiency did not increase with EENFs compared to urea-N, and some controlled release fertilisers (CRFs) decreased yield by 9–16%. Nitrification inhibitors decreased cumulative N2O emissions by 67%, while CRFs had no significant effect. Residual fertiliser N remaining in the soil at the end of the first season was strongly correlated with grain yield in the subsequent cropping year, but EENFs did not have a greater residual impact on crop growth than urea-N. The inability of EENFs to deliver increased crop N uptake or grain yield does not provide a clear case for their use as an alternative to conventional urea. [ABSTRACT FROM AUTHOR]

Background: Research translating the evidence for the benefit of mind-body exercise in older Latinos with limited access to community-based healthy aging programs is sparse. Objective: This study aimed to evaluate the feasibility of Function Improvement Exercises for Older Sedentary Community-Dwelling Latino Residents (FITxOlder), a Community Health Worker (CHW)-led, mobile technology-facilitated Chinese Qigong mind-body exercise program for healthy aging and to explore its impact on physical and cognitive function and quality of life (QoL) in older community-dwelling low-income Latino adults. Methods: This study was designed as a Stage 1 feasibility study to develop and pilot-test FITxOlder. In Phase 1 (Stage 1A), a working group of seniors, CHWs, and senior center staff guided the adaptation of Chinese Qigong into a healthy aging program. In Phase 2 (Stage 1B), 49 older Latino adults participated in a 3-arm controlled study to test the feasibility and preliminary effect of CHW-led FITxOlder on physical and cognitive function and QoL measures over 16 weeks. Results: Although the COVID-19 pandemic disrupted the implementation of the study protocol, we found favorable results regarding participant recruitment, retention, and fidelity of implementation. Notable findings included an 89.3% participant retention, 79.4% of the participants completed at least 70% of the weekly exercise goal, and no report of adverse events. The effects on intervention outcome measures were modest. Conclusions: FITxOlder is feasible for promoting healthy aging in older Latino adults; future research needs to compare its feasibility with other low-impact exercise programs for healthy aging using a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored.Research Question: Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients?Study Design and Methods: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality.Results: A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a field-based, integrated assessment of the effect of band-applied, polymer-sulfur coated urea (PSCU), plant oil coated urea (POCU), and polymer coated urea (PCU) on (i) the release dynamics of urea-N and mineral N in the soil profile (Experiment 1); and (ii) the crop N recovery and agronomic response of an irrigated maize crop (Experiment 2) relative to standard urea. Methods: Two experiments were conducted in a Vertosol under subtropical field conditions. In both experiments, six treatments (nil, urea, PSCU, POCU, and two PCU products) were replicated four times. Soil samples were collected at 8, 27, 48, 82 and 173 days after fertiliser application (DAF) to quantify N release dynamics. Maize biomass production, N uptake, grain yield and N content were quantified to assess the agronomic performance of CRFs relative to standard urea. Results: CRFs delayed the release of N relative to standard urea. Soil moisture and mass flow impacted N release dynamics from fertiliser bands, with soil chemical changes largely confined to the band for CRFs. Despite obvious differences in N release dynamics, there were no clear advantages of CRFs relative to standard urea for crop productivity and grain yield. A significant amount of in-season mineralization likely masked any potential benefits arising from the slower release of N from CRF products. Conclusion: This study improves our understanding of how CRFs behave in soil under changing environmental conditions and highlights the complexity of synchronizing N supply and crop N requirements to improve NUE in irrigated maize. [ABSTRACT FROM AUTHOR]

Objectives Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k -means CL analysis was performed. Results A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids. [ABSTRACT FROM AUTHOR]

Methane, the main component of natural gas, is an interesting source of chemicals and clean liquid fuels, and a promising alternative raw material to oil. Among the possible direct routes for methane conversion, its aromatization under non-oxidative conditions has received increasing attention, despite the low conversions obtained due to thermodynamic limitations, because of its high selectivity to benzene. Mo/H-ZSM-5, the first bifunctional zeolite-catalyst proposed for this reaction, is still considered as one of the most adequate and has been widely studied. Although the mono- or bifunctional nature of the MDA mechanism is still under debate, it is generally accepted that the Mo species activate the C-H bond in methane, producing the intermediates. These will aromatize on the Brønsted acid sites of the zeolite, whose pore dimensions will provide the shape selectivity needed for converting methane into benzene. An additional role of the zeolite's Brønsted acid sites is to promote the dispersion of the Mo oxide precursor. Here, we show the influence of the different preparation steps—metal incorporation, calcination and activation of the Mo/ZSM-5- on the metal dispersion and, therefore, on the activity and selectivity of the final catalyst. Metal dispersion is enhanced when the samples are calcined under dynamic conditions (DC) and activated in N2, and the benefits are larger when the metal has been incorporated by solid state reaction (SSR), as observed by FESEM-BSE and H2-TPR. This leads to catalysts with higher activity, increased aromatic selectivity and improved stability towards deactivation. [ABSTRACT FROM AUTHOR]

Soil constraints limit crop water and nutrient extraction and lead to yield loss globally. In rainfed agriculture, the selection of crop species more likely to yield well under constrained conditions is an important management tool. However, information on the most appropriate crops is often difficult to access due to its publication in a wide range of disparate sources and the various measures of crop tolerance used. This study aimed to improve our ability to identify crops for constrained areas in rainfed subtropical cropping systems by compiling published information that had assessed the grain yield response to acidic, saline, or sodic conditions of 17 cereal, pulse, and oilseed crops. This information was used to develop a 'traffic light' system for salinity and acidity to provide guidance on when soil pH or the electrical conductivity of a saturated soil extract (ECe) is likely to be 'good', 'potentially limiting', or 'poor' for grain yield. Crops were also ranked according to their likely ability to yield well under saline, acidic, or sodic conditions. For all crops, the point at which grain yield was affected by soil constraints was variable and there was often only a small amount of published information available to help guide the identification of tolerance limits and rankings, particularly for sodicity. Many studies were also conducted under experimental conditions that differed from rainfed farming, which can affect the transferability of results. Confidence in the tolerance limits and rankings is thus only moderate and further work is required to confirm their applicability. [ABSTRACT FROM AUTHOR]

Background Data on the activation of the acute inflammatory response and its clinicopathological associations in idiopathic nephrotic syndrome (INS) are scarce and discordant. Objective To analyse the associations between the activation of the inflammatory response, the clinicopathological characteristics of disease and the response to treatment with steroids in patients with INS. Methods A total of 101 patients with INS due to minimal change disease (MCD; n = 44), focal segmental glomerulosclerosis (FSGS; n = 33) and membranous nephropathy (MN; n = 24) and 50 healthy controls were included. At diagnosis, we measured the levels of haemopexin (Hx), haptoglobin (Hgl), interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), tumour necrosis factor-α (TNF-α), soluble IL-1 receptor, interferon-γ and C-reactive protein. We analysed their clinicopathological associations. In MCD and FSGS patients, we determined the association between the levels of these variables and steroid resistance. Results The levels of Hx, Hgl, TNF-α, suPAR and IL-6 were higher in patients with INS than in healthy controls, and were not associated with proteinuria, estimated glomerular filtration rate or serum albumin. In MCD and FSGS patients, Hx, Hgl, IL-6 and TNF-α levels were similar and significantly higher than in MN patients. In patients with MCD and FSGS, multivariate analyses identified FSGS and the levels of Hx, Hgl or IL-6 as independent predictors of steroid resistance. Conclusions The activation of the inflammatory response in patients with INS is heterogeneous and more prevalent in MCD or FSGS patients than in those with MN. In MCD and FSGS, elevated levels of Hx, Hgl or IL-6 are independently associated with steroid resistance. [ABSTRACT FROM AUTHOR]

Aims/Purpose: Triplet repeat expansion‐mediated endothelial corneal dystrophy, including Fuchs endothelial corneal dystrophy (FECD), is characterized by abnormal expansions of trinucleotide repeats, resulting in corneal endothelium dysfunction [1,2]. This study aims to characterize a reliable in vivo model, that it lacks, and explore the therapeutic potential of anti‐miRs, which have shown efficacy in other disorders involving triplet repeat expansions [3,4,5]. Current invasive delivery methods for eye‐based treatments present challenges, so our focus is on optimizing non‐invasive delivery methods for anti‐miR‐based therapy. Methods: A transgenic mouse model with a significant CTG repeat expansion (>1000), established in DM1, was investigated as an in vivo model for corneal endothelial dystrophy. The Fuchs‐like phenotype of the disease was characterized using immunohistochemistry and FISH techniques. Delivery methods were explored to enhance the targeting of corneal endothelial cells (CEC). Delivery efficacy and marker expression were assessed using fluorescence, RT‐qPCR, PCR, western blotting, and immunocytochemistry techniques. FECD cell cultures were established to evaluate the challenging FECD‐specific delivery systems. Results: A novel in vivo model has been characterized for studying corneal endothelial dystrophy caused by triplet repeat expansion, exhibiting similarities to the Fuchs‐like phenotype. Enhanced delivery methods have been identified to improve transfection efficiency in endothelial (HUVEC) and CEC. Successful establishment of FECD cell cultures has allowed the evaluation of these enhanced delivery systems. Conclusions: The first successful characterization of an in vivo model for triplet repeat expansion‐mediated corneal endothelial dystrophy has been achieved. This model shows potential for assessing the reversal of these phenotypes in the ocular region. Moreover, the successful delivery of new systems across CEC suggests the possibility of non‐invasive administration of anti‐miR directly into the eye. This breakthrough opens the door for future research on anti‐miRs in other diseases caused by triplet repeat expansion, such as FECD. Reference In PMID: [1] 28886202, [2] 34130750, [3] 29946070, [4] 32805487, [5] 22764244. [ABSTRACT FROM AUTHOR]

Emotional dysregulation, age, gender, and obesity are transdiagnostic risk factors for the development and maintenance of eating disorders (EDs). Previous studies found that patients with ED had less meaning in life than the non-clinical population, and that meaning in life acted as a buffer in the course of ED; however, to the data, there are no studies about the mediator role of meaning in life in association between the emotional dysregulation and the ED psychopathology. Objective: To analyze the mediating role of meaning in life in the relationship between emotional dysregulation and the ED psychopathology in three samples with diverse risk factors for ED. Method: Sample 1, n = 153 undergraduate young women; sample 2, n = 122 participants with obesity; and sample 3, n = 292 participants with ED. Multiple mediation analysis was performed. Results: Sample 1: meaning in life showed a mediation effect between emotional dysregulation and the ED psychopathology (direct effect β = 0.390, p < 0.05) (indirect effect β = 0.227, p < 0.05), body satisfaction (direct effect β = −0.017, p < 0.05) (indirect effect β = −0.013, p < 0.01), and depression symptoms (direct effect β = 1.112, p < 0.001) (indirect effect β = 0.414, p < 0.001); sample 2: meaning in life showed a mediation effect between emotional dysregulation and binge eating and purging behaviors (direct effect β = 0.194, p < 0.01) (indirect effect β = 0.054, p < 0.05) and depression symptoms (direct effect β = 0.357, p < 0.001) (indirect effect β = 0.063, p < 0.05); sample 3: meaning in life showed a mediation effect between emotional dysregulation and the ED psychopathology (direct effect β = 0.884, p < 0.001) (indirect effect β = 0.252, p < 0.007), body satisfaction (direct effect β = −0.033, p < 0.05) (indirect effect β = −0.021, p < 0.001), borderline symptoms (direct effect β = 0.040, p < 0.001) (indirect effect β = 0.025, p < 0.001), and hopelessness (direct effect β = 0.211, p < 0.001) (indirect effect β = 0.087, p < 0.001). Conclusions: These studies suggest the importance of considering meaning in life as a variable in the onset and maintenance of ED. [ABSTRACT FROM AUTHOR]

Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, <75 represents healthy subjects, p < 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (p < 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (p < 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (p < 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different. [ABSTRACT FROM AUTHOR]

The interaction between brain damage and motor function is not yet fully understood in children with spastic cerebral palsy (CP). Therefore, a semi-quantitative MRI (sqMRI) scale was used to explore whether identified brain lesions related to functional abilities and gait pathology in this population. A retrospective cohort of ambulatory children with spastic CP was selected [ N = 104; 52 bilateral (bCP) and 52 unilateral (uCP)]. Extent and location-specific scores were defined according to the sqMRI scale guidelines. The gross motor function classification system (GMFCS), the gait profile score (GPS), GPSs per motion plane, gait variable scores (GVS) and multiple-joint (MJ) gait patterns were related to brain lesion scores. In all groups, the global total brain scores correlated to the GPS (total: r s = 0.404, p ≤ 0.001; bCP: r s = 0.335, p ≤ 0.05; uCP: r s = 0.493, p ≤ 0.001). The global total hemispheric scores correlated to the GMFCS (total: r s = 0.392, p ≤ 0.001; bCP: r s = 0.316, p ≤ 0.05; uCP: r s = 0.331, p ≤ 0.05). The laterality scores of the hemispheres in the total group correlated negatively to the GMFCS level (r s = −0.523, p ≤ 0.001) and the GVS-knee sagittal (r s = −0.311, p ≤ 0.01). Lesion location, for the total group demonstrated positive correlations between parietal lobe involvement and the GPS (r s = 0.321, p ≤ 0.001) and between periventricular layer damage and the GMFCS (r s = 0.348, p ≤ 0.001). Involvement of the anterior part of the corpus callosum (CC) was associated with the GVS-hip sagittal in all groups (total: r pb = 0.495, p ≤ 0.001; bCP: r pb = 0.357, p ≤ 0.05; uCP: r pb = 0.641, p ≤ 0.001). The global total hemispheric and laterality of the hemispheres scores differentiated between the minor and both the extension (p ≤ 0.001 and p ≤ 0.001) and flexion (p = 0.016 and p = 0.013, respectively) MJ patterns in the total group. Maximal periventricular involvement and CC intactness were associated with extension patterns (p ≤ 0.05 and p ≤ 0.001, respectively). Current findings demonstrated relationships between brain structure and motor function as well as pathological gait, in this cohort of children with CP. These results might facilitate the timely identification of gait pathology and, ultimately, guide individualized treatment planning of gait impairments in children with CP. [ABSTRACT FROM AUTHOR]

Modified constraint-induced movement therapy (mCIMT) improves upper limb (UL) motor execution in unilateral cerebral palsy (uCP). As these children also show motor planning deficits, action-observation training (AOT) might be of additional value. Here, we investigated the combined value of AOT to mCIMT on UL kinematics in children with uCP in a randomized controlled trial. Thirty-six children with uCP completed an UL kinematic and clinical evaluation after participating in a 9-day mCIMT camp wearing a splint for 6 h/day. The experimental group (mCIMT + AOT, n = 20) received 15 h of AOT, i.e. video-observation and execution of unimanual tasks. The control group (mCIMT + placebo, n = 16) watched biological-motion free videos and executed the same tasks. We examined changes in motor control (movement duration, peak velocity, time-to-peak velocity, and trajectory straightness) and kinematic movement patterns (using Statistical Parametric Mapping) during the execution of three unimanual, relevant tasks before the intervention, after and at 6 months follow-up. Adding AOT to mCIMT mainly affected movement duration during reaching, whereas little benefit is seen on UL movement patterns. mCIMT, with or without AOT, improved peak velocity and trajectory straightness, and proximal movement patterns. Clinical and kinematic improvements are poorly related. Although there seem to be limited benefits of AOT to CIMT on UL kinematics, our results support the inclusion of kinematics to capture changes in motor control and movement patterns of the proximal joints. [ABSTRACT FROM AUTHOR]