Morphological and pathogenic investigation of the emerging fungal threat Emergomyces africanus.

Emergomyces africanus is a highly fatal fungal pathogen affecting individuals with advanced HIV disease. Molecular patterns and ultrastructural aspects of E. africanus are unknown, and pathogenic models have not been investigated in detail. Since the cell wall of fungi is a determinant for interaction with the host and antifungal development, we characterized the ultrastructural aspects of E. africanus and the general properties of cell wall components under different conditions of growth in vitro and in vivo. We also tested the pathogenic potential of E. africanus in a Galleria mellonella model of infection. Transmission electron microscopy revealed the common intracellular, ultrastructural features of fungi in association with a thick cell wall. Scanning electron microscopy revealed a smooth cell surface, with no apparent decorative structures. Yeast cultures of E. africanus showed the distribution of chitin, chitooligomers, and mannoproteins commonly observed in fungi. However, in mixed microenvironments containing yeast and filamenting forms of E. africanus, the detection of chitooligomers was increased in comparison with isolated yeast cells, while the detection of these components in filamenting forms was markedly reduced. These observations were suggestive of the ability of E. africanus to change its cell wall composition in response to different microenvironments. Although E. africanus was unable to kill G. mellonella, this infection model allowed us to isolate infected hemocytes for further analysis of mannoproteins, chitin, and chitooligomers. Once again, the detection of E. africanus chitooligomers was markedly increased. These results reveal previously unknown ultrastructural features of E. africanus and suggest a high plasticity in the cell wall of this lethal pathogen. IMPORTANCE: The epidemiology of fungal infections is very dynamic, and novel health emergencies are hard to predict. New fungal pathogens have been continuously emerging for the last few decades, and Emergomyces africanus is one of these threats to human health. This complex scenario points to the need for generating knowledge about emerging pathogens so that new therapeutic strategies can be designed. In this study, we characterized the general cellular and pathogenic properties of the emerging fungal pathogen E. africanus. Our results reveal that E. africanus manifests some of the typical properties of fungal cells but also exhibits some unique characteristics that might be helpful for the future development of therapeutic strategies.

Grief Coach: Feasibility and acceptability of a text message program for bereavement support among grievers in the United Kingdom.

To address gaps in bereavement services in the UK, a national charity offered free access to Grief Coach, a 12-month text message-based grief support program. To assess the feasibility and acceptability of the approach, this study examined program reach, retention, and user satisfaction. Over 4000 grievers enrolled in the program over 13.5 months; 6- and 12-month retention rates were 87.8% and 83.2%. Among individuals responding to a satisfaction survey (response rate = 55.9%), 94.8% rated the program as moderately or very helpful and 95.4% said it contributed to their sense of being supported in their grief. Common themes emerging from a qualitative analysis of the written comments were how the program helped with coping with the pain of grief and user appreciation of the program. Grief Coach may be a promising component of high-quality grief support to meet the needs of grieving people in the UK.

The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.

Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid-tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75-80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell-cell adhesion, cell-substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, CLU gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch's corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.

SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice.

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro. In vivo, topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells.

Assessing Pediatric Mild Traumatic Brain Injury and Its Recovery Using Resting-State Magnetoencephalography Source Magnitude Imaging and Machine Learning.

The objectives of this machine-learning (ML) resting-state magnetoencephalography (rs-MEG) study involving children with mild traumatic brain injury (mTBI) and orthopedic injury (OI) controls were to define a neural injury signature of mTBI and to delineate the pattern(s) of neural injury that determine behavioral recovery. Children ages 8-15 years with mTBI (n = 59) and OI (n = 39) from consecutive admissions to an emergency department were studied prospectively for parent-rated post-concussion symptoms (PCS) at: 1) baseline (average of 3 weeks post-injury) to measure pre-injury symptoms and also concurrent symptoms; and 2) at 3-months post-injury. rs-MEG was conducted at the baseline assessment. The ML algorithm predicted cases of mTBI versus OI with sensitivity of 95.5 ± 1.6% and specificity of 90.2 ± 2.7% at 3-weeks post-injury for the combined delta-gamma frequencies. The sensitivity and specificity were significantly better (p < 0.0001) for the combined delta-gamma frequencies compared with the delta-only and gamma-only frequencies. There were also spatial differences in rs-MEG activity between mTBI and OI groups in both delta and gamma bands in frontal and temporal lobe, as well as more widespread differences in the brain. The ML algorithm accounted for 84.5% of the variance in predicting recovery measured by PCS changes between 3 weeks and 3 months post-injury in the mTBI group, and this was significantly lower (p < 10-4) in the OI group (65.6%). Frontal lobe pole (higher) gamma activity was significantly (p < 0.001) associated with (worse) PCS recovery exclusively in the mTBI group. These findings demonstrate a neural injury signature of pediatric mTBI and patterns of mTBI-induced neural injury related to behavioral recovery.

Emotional Appetite Questionnaire: psychometric properties in Brazilian adult samples before and after the COVID-19 pandemic onset.

Background: Appetite represents a desire of a person to eat specific food in order to reach satisfaction and pleasure states. This desire may be associated with the experience of negative or positive emotions (emotional appetite). Emotional appetite can influence eating behavior, and its investigation is relevant to avoid possible damage to health resulting from a disordered eating. Objectives: To adapt the Emotional Appetite Questionnaire (EMAQ) to the Portuguese language; to assess the validity and reliability of the data; and to assess emotional appetite in three samples of adults collected before and after the outbreak of the COVID-19 pandemic. Methods: This is a cross-sectional study with non-probabilistic convenience sampling. The Portuguese version of the EMAQ was presented after translation, back-translation, and content analysis. Two studies were conducted, the first before and the second after the pandemic onset. Three samples were formed (2019: Sample 1 (age = 19.7 ± 1.5 years) n = 323; 2020: Sample 2 (age = 21.3 ± 1.8 years) n = 1,011; and Sample 3 (age = 28.9 ± 3.1 years) n = 909). An exploratory strategy with parallel analysis was performed. The analyses were conducted in FACTOR and R (lavaan and semTools packages) software. After determining the best-fit model for the data, emotional appetite was examined considering decrease, non-alteration, and increase in appetite in the face of positive and negative emotions/situations. The profile of emotional appetite was determined using a circumplex model. Results: The two-factor model described by the valence of emotions/situations fitted the samples (Comparative Fit Indexminimum-maximum = 0.95-0.98; Tucker-Lewis Index = 0.94-0.98; Root Mean Square Error of Approximation = 0.03-0.08; αord = 0.78-0.88). Increases in appetite were more frequent for positive emotions/situations (52.0-57.5%), and both decreases (35.4-44.5%) and increases (50.0-56.2%) in appetite were observed for negative emotions/situations. Emotions with negative valence and activation were more relevant to appetite reduction, while a significant increase in appetite was observed with anxiety (negative valence and positive activation). Conclusion: Different emotions and situations may influence appetite in people, and such an investigation may be useful in preparing eating protocols.

Isolation and Molecular Characterization of Two Novel Lytic Bacteriophages for the Biocontrol of Escherichia coli in Uterine Infections: In Vitro and Ex Vivo Preliminary Studies in Veterinary Medicine.

E. coli is one of the etiological agents responsible for pyometra in female dogs, with conventional treatment involving ovariohysterectomy. Here, we report the isolation and full characterization of two novel lytic phages, viz. vB_EcoM_Uniso11 (ph0011) and vB_EcoM_Uniso21 (ph0021). Both phages belong to the order Caudovirales and present myovirus-like morphotypes, with phage ph0011 being classified as Myoviridae genus Asteriusvirus and phage ph0021 being classified as Myoviridae genus Tequatrovirus, based on their complete genome sequences. The 348,288 bp phage ph0011 and 165,222 bp phage ph0021 genomes do not encode toxins, integrases or antimicrobial resistance genes neither depolymerases related sequences. Both phages were shown to be effective against at least twelve E. coli clinical isolates in in vitro antibacterial activity assays. Based on their features, both phages have potential for controlling pyometra infections caused by E. coli. Phage ph0011 (reduction of 4.24 log CFU/mL) was more effective than phage ph0021 (reduction of 1.90 log CFU/mL) after 12 h of incubation at MOI 1000. As a cocktail, the two phages were highly effective in reducing the bacterial load (reduction of 5.57 log CFU/mL) at MOI 100, after 12 h of treatment. Both phages were structurally and functionally stabilized in vaginal egg formulations.

Influence of Different Heat-Stress-Reducing Systems on Physiological and Behavioral Responses and Social Dominance of Holstein and Jersey Cows and Heifers on Pasture.

High ambient temperatures and relative humidity affect the behavior and physiology of the animal. This study investigated the influence of different heat-stress-reducing systems on the physiological, behavioral, and preferential responses of Holstein and Jersey cows and heifers on pasture. Experimental treatments were: (1) three heat-stress-reducing systems (sprinklers + artificial shade; showers + artificial shade; and artificial shade); (2) two breeds (Holstein and Jersey); and (3) two physiological stages (lactating cows and pubertal heifers). Physiological and behavioral responses to treatments were measured every 30 min on collection days. The frequency and duration of the use of the systems were recorded continuously 24 h/day for 3 days in each period. The air temperature and the relative humidity were 26 ± 4.1 °C and 74 ± 11.3%, respectively. The experimental treatments affected (p = 0.0354) standing idle, grazing behavior (p = 0.0435), and the frequency and duration of use of the systems by the animals (p < 0.0001). For all treatments, the respiratory rate and the coat surface temperature were highly and significantly correlated (p < 0.05) with the temperature and humidity index. In conclusion, under ambient conditions, dairy cows preferred using sprinklers or showers over artificial shade. These systems were more efficient at reducing the heat load and led to better behavioral and physiological responses.

Isolation and Molecular Characterization of a Novel Lytic Bacteriophage That Inactivates MDR Klebsiella pneumoniae Strains.

The worldwide increase in serious infections caused by multidrug-resistant (MDR) K. pneumoniae emphasizes the urgent need of new therapeutic strategies for the control of this pathogen. There is growing interest in the use of bacteriophages (or phages) to treat K. pneumoniae infections, and newly isolated phages are needed. Here, we report the isolation and physical/biological/molecular characterization of a novel lytic phage and its efficacy in the control of MDR K. pneumoniae. The phage vB_KpnS_Uniso31, referred to hereafter as phage Kpn31, was isolated from hospital wastewater using K. pneumoniae CCCD-K001 as the host. Phage Kpn31 presents a siphovirus-like morphotype and was classified as Demerecviridae; Sugarlandvirus based on its complete genome sequence. The 113,444 bp Kpn31 genome does not encode known toxins or antimicrobial resistance genes, nor does it encode depolymerases related sequences. Phage Kpn31 showed an eclipse time of 15 min and a burst size of 9.12 PFU/host cell, allowing us to conclude it replicates well in K. pneumoniae CCCD-K001 with a latency period of 30 min. Phage Kpn31 was shown to be effective against at least six MDR K. pneumoniae clinical isolates in in vitro antibacterial activity assays. Based on its features, phage Kpn31 has potential for controlling infections caused by MDR K. pneumoniae.

Oral administration of botryosphaeran [(1 → 3)(1 → 6)-ß-d-glucan] reduces inflammation through modulation of leukocytes and has limited effect on inflammatory nociception.

Several biological activities of the fungal exopolysaccharide (1 → 3)(1 → 6)-ß-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal ß-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal ß-glucan a new possibility for complementary treating acute and chronic inflammation.

Cytokine profile and cholesterol levels in patients with Niemann-Pick type C disease presenting neurological symptoms: in vivo effect of miglustat and in vitro effect of N-acetylcysteine and coenzyme Q10.

Niemann Pick type C is an inborn error of metabolism (IEM), classified as a lysosomal storage disease (LSD) caused by a dysfunction in NPC transport protein, that leads to intracellular accumulation of non-esterified cholesterol and other lipids. Clinical manifestations are ample, with visceral and neurological symptoms. Miglustat, a molecule that reversibly inhibits glucosylceramide synthase is used as treatment for this disorder. Studies demonstrated the influence of oxidative stress and inflammation in IEM, as well in animal model of NP-C disease. Nonetheless, literature lacks data on patients, so our work aimed to investigate if there is influence of chronic inflammation in the pathophysiology of NP-C disease, and the effect of miglustat, N-acetylcysteine (NAC) and Coenzyme Q10 (CoQ10). We evaluated the plasmatic cytokines in NPC patients at diagnosis and during the treatment with miglustat. Additionally, we performed an in vitro study with antioxidants NAC (1 mM and 2.5 mM) and CoQ10 (5 µM and 10 µM), where we could verify its effect on inflammatory parameters, as well as in cholesterol accumulation. Our results showed that NP-C patients have higher plasmatic levels of pro and anti-inflammatory cytokines (IL-6, IL-8, and IL-10) at diagnosis and the treatment with miglustat was able to restore it. In vitro study showed that treatment with antioxidants in higher concentrations significantly decrease cholesterol accumulation, and NAC at 2.5 mM normalized the level of pro-inflammatory cytokines. Although the mechanism is not completely clear, it can be related to restoration in lipid traffic and decrease in oxidative stress caused by antioxidants.

Estimating changes in emergency department visits associated with floods caused by Tropical Storm Imelda using satellite observations and syndromic surveillance.

BACKGROUND: Satellite observations following flooding coupled with electronic health data collected through syndromic surveillance systems (SyS) may be useful in efficiently characterizing and responding to health risks associated with flooding. RESULTS: There was a 10% (95% Confidence Interval (CI): 1%-19%) increase in asthma related ED visits and 22% (95% CI: 5%-41%) increase in insect bite related ED visits in the flooded ZCTAs compared to non-flooded ZCTAs during the flood period. One month following the floods, diarrhea related ED visits were increased by 15% (95% CI: 4%-27%) for flooded ZCTAs and children and adolescents from flooded ZCTAs had elevated risk for dehydration related ED visits. During the protracted period (2-3 months after the flood period), the risk for asthma, insect bite, and diarrhea related ED visits were elevated among the flooded ZCTAs. Effect modification by reported age, ethnicity and race was observed. CONCLUSION: Combining satellite observations with SyS data can be helpful in characterizing the location and timing of environmentally mediated adverse health outcomes, which may be useful for refining disaster resilience measures to mitigate health outcomes following flooding.

Does neural face processing explain effects of an attachment-based intervention on maternal sensitivity? A randomized controlled study including pre- and postintervention measures.

BACKGROUND: Although there is a large body of literature highlighting the behavioral effects of parenting interventions, studies on the neurocognitive mechanisms involved in such intervention effects remain scarce. PURPOSE: The aim of the current study was to test whether changes in neural face processing (as reflected in N170 amplitudes) would act as a mediator in the association between the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) and maternal sensitivity. METHODS: A total of 66 mothers of whom a random 33% received the VIPP-SD and the others a "dummy" intervention participated in pre- and postintervention assessments. We recorded mothers' electroencephalographic (EEG) activity in response to photographs of children's neutral, happy, and angry facial expressions. Maternal sensitivity was observed while mothers interacted with their offspring in a semi-structured play situation. RESULTS: In contrast with our expectations, we did not find evidence for mediation of intervention effects on maternal sensitivity by the N170. CONCLUSION: We discuss that parenting support programs may yield different effects on neurocognitive processes depending on the population and provide recommendations for future research. Our study underscores the importance of reporting null findings and preregistering studies in the field of neurocognitive research.

Does maternal inhibitory control mediate effects of a parenting intervention on maternal sensitive discipline? Evidence from a randomized-controlled trial.

The quality of parenting greatly impacts child development, highlighting the importance of support programs that effectively improve parenting. Studies on successful intervention programs define their efficacy by gains in parenting and/or child development. However, much remains unknown about the internal processes that explain how parenting interventions bring about their effects. The aims of the current randomized-controlled study were to test whether the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) improved maternal inhibitory control (1) and whether inhibitory control mediated any effects of VIPP-SD on maternal sensitive discipline (2). In total, 66 mothers of whom a random 33% received the VIPP-SD and the others a "dummy" intervention participated in pre- and post-intervention assessments. Sensitive discipline was observed during a semi-structured limit-setting situation and inhibitory control was measured using a stop-signal task. Contrary to expectations, inhibitory control improved over time in the control group and sensitive discipline did not show the expected increase in the intervention group. Results did not support mediation. We suggest that the intervention may have induced cognitive restructuring of parenting schemas, delaying improvements in post-intervention inhibitory control and sensitive discipline. Factors that may be involved in parents' susceptibility to interventions require attention in future work.

La calidad de la crianza tiene gran impacto en el desarrollo del niño, lo cual enfatiza la importancia de programas de apoyo que efectivamente mejoran la crianza. Los estudios sobre programas de intervención exitosa definen su efectividad según los logros en la crianza y/o el desarrollo del niño. Sin embargo, aún se desconoce mucho acerca de los procesos internos que explican cómo las intervenciones de crianza producen sus resultados. Las metas del presente estudio controlado al azar fueron examinar si la Intervención de Informe de Video para promover una Crianza Positiva y una Disciplina Sensible (VIPP-SD) mejoraba el control inhibitorio materno (1) y si el control inhibitorio mediaba cualesquiera efectos de VIPP-SD sobre la sensible disciplina materna (2). En total, 66 madres participaron en las evaluaciones anteriores y posteriores a la intervención; de ellas el 33% -escogidas al azar- recibió la VIPP-SD y las demás una intervención "ficticia." Se observó la disciplina sensible durante una situación semiestructurada limitada a un espacio y el control inhibitorio se midió usando una tarea con una señal de detenerse. Contrario a las expectativas, el control inhibitorio mejoró a lo largo del tiempo en el grupo de control y la disciplina sensible no mostró el esperado incremento en el grupo de intervención. Los resultados no apoyaron la mediación. Sugerimos que la intervención pudiera haber generado una restructuración cognitiva de esquemas de crianza, demorando la mejoría en el control inhibitorio y la disciplina sensible en la post intervención. Los factores que pudieran estar relacionados con la susceptibilidad de los progenitores a las intervenciones requieren atención en el trabajo futuro.

La qualité du parentage affecte énormément le développement de l'enfant, mettant en lumière l'importance des programmes de soutien qui améliorent le parentage de manière efficace. Des études sur des programmes d'intervention définissent leur efficacité par les gains dans le parentage et/ou le développement de l'enfant. Cependant il reste beaucoup à apprendre sur les processus internes qui expliquent comment l'impact des interventions de parentage. Les buts de cette étude randomisée contrôlée étaient de tester si l'intervention de rétroaction vidéo destinée à promouvoir un Parentage Positif et la Discipline Sensible (VIPP-SD en anglais) améliorait le contrôle inhibitoire maternel (1) et si le contrôle inhibitoire induisait des effets du VIPP-SD sur la discipline sensible maternelle (2). En tout 66 mères dont 33% au hasard ont reçu le VIPP-SE et les autres une intervention « factice ¼ ont participé à des évaluations pré- et post-intervention. La discipline sensible a été observée durant une situation semi-structurée de réglage de limites et le contrôle inhibitoire a été mesuré en utilisant un exercice de signal d'arrêt. Contrairement aux attentes le contrôle inhibitoire s'est amélioré au fil du temps dans le groupe contrôle et la discipline sensible n'a pas fait preuve de l'augmentation escomptée dans le groupe d'intervention. Les résultats de soutiennent pas la médiation. Nous suggérons que l'intervention pourrait avoir déclenché une restructuration cognitive des schémas de parentage, retardant les améliorations dans le contrôle inhibitoire post-intervention et la discipline sensible. Les facteurs qui peuvent être impliqués dans la susceptibilité des parents aux interventions exigent de l'attention pour le travail à venir.

Crotalphine Attenuates Pain and Neuroinflammation Induced by Experimental Autoimmune Encephalomyelitis in Mice.

Multiple sclerosis (MS) is a demyelinating disease of inflammatory and autoimmune origin, which induces sensory and progressive motor impairments, including pain. Cells of the immune system actively participate in the pathogenesis and progression of MS by inducing neuroinflammation, tissue damage, and demyelination. Crotalphine (CRO), a structural analogue to a peptide firstly identified in Crotalus durissus terrificus snake venom, induces analgesia by endogenous opioid release and type 2 cannabinoid receptor (CB2) activation. Since CB2 activation downregulates neuroinflammation and ameliorates symptoms in mice models of MS, it was presently investigated whether CRO has a beneficial effect in the experimental autoimmune encephalomyelitis (EAE). CRO was administered on the 5th day after immunization, in a single dose, or five doses starting at the peak of disease. CRO partially reverted EAE-induced mechanical hyperalgesia and decreased the severity of the clinical signs. In addition, CRO decreases the inflammatory infiltrate and glial cells activation followed by TNF-α and IL-17 downregulation in the spinal cord. Peripherally, CRO recovers the EAE-induced impairment in myelin thickness in the sciatic nerve. Therefore, CRO interferes with central and peripheral neuroinflammation, opening perspectives to MS control.

Three-Month Psychiatric Outcome of Pediatric Mild Traumatic Brain Injury: A Controlled Study.

The objective was to clarify occurrence, phenomenology, and risk factors for novel psychiatric disorder (NPD) in the first 3 months after mild traumatic brain injury (mTBI) and orthopedic injury (OI). Children aged 8-15 years with mTBI (n = 220) and with OI but no TBI (n = 110) from consecutive admissions to an emergency department were followed prospectively at baseline and 3 months post-injury with semi-structured psychiatric interviews to document the number of NPDs that developed in each participant. Pre-injury child variables (adaptive, cognitive, and academic function, and psychiatric disorder), pre-injury family variables (socioeconomic status, family psychiatric history, and family function), and injury severity were assessed and analyzed as potential confounders and predictors of NPD. NPD occurred at a significantly higher frequency in children with mTBI versus OI in analyses unadjusted (mean ratio [MR] 3.647, 95% confidence interval [CI95] (1.264, 15.405), p = 0.014) and adjusted (MR = 3.724, CI95 (1.264, 15.945), p = 0.015) for potential confounders. In multi-predictor analyses, the factors besides mTBI that were significantly associated with higher NPD frequency after adjustment for each other were pre-injury lifetime psychiatric disorder [MR = 2.284, CI95 (1.026, 5.305), p = 0.043]; high versus low family psychiatric history [MR = 2.748, CI95 (1.201, 6.839), p = 0.016], and worse socio-economic status [MR = 0.618 per additional unit, CI95 (0.383, 0.973), p = 0.037]. These findings demonstrate that mild injury to the brain compared with an OI had a significantly greater deleterious effect on psychiatric outcome in the first 3 months post-injury. This effect was present even after accounting for specific child and family variables, which were themselves independently related to the adverse psychiatric outcome.

Sex differences in the behavioral and immune responses of mice to tumor growth and cancer therapy.

There is significant variability in the expression of cancer-related fatigue. Understanding the factors that account for this variation provide insight into the underlying mechanisms. One important, but often overlooked, variable is biological sex. While a few clinical studies have indicated that female patients report higher levels of fatigue, these studies are subject to potential socio-culture reporting biases. Only a limited number of preclinical studies have considered sex differences in animal model of fatigue and few have simultaneously considered both disease- and treatment-related factors. The present series of studies was initiated to address the current knowledge gap on the importance of sex differences in cancer-related fatigue. We selected a murine model of human papilloma virus-positive head and neck cancer based on heterotypic injection of the mEERL95 cell line that grows in both male and female mice and responds to a regimen of cisplatin plus irradiation. We also tested the impact of immunotherapy treatment targeting PD1. Voluntary wheel running was used to evaluate fatigue-like behavior. Male mice grew larger tumors than did female mice and showed more severe fatigue-like behavior. We confirmed that the tumor increased the expression of inflammatory cytokines in the liver, but no sex differences were observed. As a trend toward elevated Cd3 mRNA was observed in female mice, we tested the importance of T cells using female Rag2-/- mice. The Rag2-/- female mice had accelerated tumor growth and more severe fatigue-like behavior. In response to cisplatin alone non-tumor-bearing female mice showed a slower recovery of wheel running activity compared to males. However, in response to chemoradiation and anti-PD1 neutralizing antibody, tumor-bearing female mice showed a better tumor response to therapy than male mice, but no significant sex differences were observed for wheel running. These findings point to different mechanisms underlying tumor- and treatment-induced behavioral fatigue and indicate that the sex factor can intervene to modulate the expression of fatigue-like behavior in particular circumstances.

Hydrogel from all in all lignocellulosic sisal fibers macromolecular components.

The heterogeneous structure of lignocellulosic biomass makes it difficult to dissolve its main components (cellulose, hemicelluloses, and lignin) by solvent action with the aim of further applying the mixture of the biological macromolecules generated in the solvent medium. In the present study, the dissolution efficiency (DE) of lignocellulosic sisal fibers in the lithium chloride/dimethylacetamide solvent system (LiCl/DMAc) was evaluated for further application in the formation of hydrogels. Catalytic amounts of trifluoroacetic acid (TFA) were used in some experiments, which increased the DE from 40% to 90%. The regeneration of the solutions, either previously filtered or not, led to hydrogels based on sisal lignocellulosic biomass. In brief, the properties of the hydrogels were influenced by the content of the lignocellulosic components in the hydrogels, present both in the dissolved fraction and in the incorporated undissolved fraction (when nonfiltered solutions were used). Hydrogels presented water absorption up to 7479% and resorption content in the lyophilized hydrogel up to 2133%. Extracts obtained from preselected hydrogels exhibited cell viability up to 127% compared to the control group when in contact with fibroblast cultures, exhibiting their noncytotoxic properties. This attribute increased the range of possible applications of these hydrogels, ranging from agriculture to biocompatible materials.