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1.
Sci Rep ; 14(1): 11660, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38777847

ABSTRACT

The presence of Salmonella in dry fermented sausages is source of recalls and outbreaks. The genomic diversity of 173 Salmonella isolates from the dry fermented sausage production chains (pig carcasses, pork, and sausages) from France and Spain were investigated through their core phylogenomic relationships and accessory genome profiles. Ten different serovars and thirteen sequence type profiles were identified. The most frequent serovar from sausages was the monophasic variant of S. Typhimurium (1,4,[5],12:i:-, 72%) while S. Derby was in pig carcasses (51%). Phylogenomic clusters found in S. 1,4,[5],12:i:-, S. Derby, S. Rissen and S. Typhimurium serovars identified closely related isolates, with less than 10 alleles and 20 SNPs of difference, displaying Salmonella persistence along the pork production chain. Most of the S. 1,4,[5],12:i:- contained the Salmonella genomic island-4 (SGI-4), Tn21 and IncFIB plasmid. More than half of S. Derby strains contained the SGI-1 and Tn7. S. 1,4,[5],12:i:- genomes carried the most multidrug resistance genes (91% of the strains), whereas extended-spectrum ß-lactamase genes were found in Typhimurium and Derby serovars. Salmonella monitoring and characterization in the pork production chains, specially S. 1,4,[5],12:i:- serovar, is of special importance due to its multidrug resistance capacity and persistence in dry fermented sausages.


Subject(s)
Food Microbiology , Meat Products , Phylogeny , Salmonella , Meat Products/microbiology , Spain , France , Animals , Salmonella/genetics , Salmonella/isolation & purification , Salmonella/classification , Swine , Fermentation , Genome, Bacterial , Serogroup , Genomics/methods , Genomic Islands/genetics
2.
Front Sports Act Living ; 6: 1372664, 2024.
Article in English | MEDLINE | ID: mdl-38596641

ABSTRACT

Objective: To determine if the active methodology for improving sports initiation (M.A.M.I.deporte®) shared between children and parents successfully promotes children in sports activities, maintains their activity and improves long-term adherence. Participants: The study involved 118 participants aged between 2 and 11 years (6.3 ± 2.3). In the first season, 34 participated (16 girls; 18 boys); in the second season, 46 participated (22 girls; 24 boys) and in the third season, 38 participated (19 girls; 19 boys). Methodology: It was carried out from October to June over three academic years for two hours a week. Every 4 sessions a different sporting activity was carried out, planned so that parents and children could practise them, simultaneously. Analysis: At the beginning and end of each period, a survey was carried out on the sports activities in which the participants had started. If participants remained in the activity, the survey was face-to-face and if participants no longer attended the activity, they were contacted by telephone. Descriptive values were obtained for the variables in absolute and percentage form and a repeated measures anova was performed. Results: Vigorous physical activity performed was 3.82 ± 1.16 h/week in the first year, 3.38 ± 1.59 in the second year and 2.99 ± 1.46 in the third year with no significant differences between any of the years. 32.20% joined other sporting activities and only 6.78% gave up vigorous physical activity. Conclusion: Joint activity of parents and children contributed to maintaining vigorous physical activity at the recommended levels in the child population with only 6.78% (n = 8) of the participants dropping out.

3.
Gait Posture ; 108: 90-96, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38016398

ABSTRACT

BACKGROUND: Basketball is a team sport in which players perform multidirectional movements, jumps and landings, experiencing abrupt accelerations and decelerations and numerous changes of rhythm. In this sport, speed and intensity are two key factors that are associated with an increased risk of injury. The aim of this randomized controlled trial was to determine the effectiveness of a specific gluteus maximus strength programme as preventive work for young female basketball players, to improve dynamic postural stability and to observe its impact in the rate of lower limb injuries, vertical jump, dynamic knee valgus and pain. RESEARCH QUESTION: Is effective a strength programme to improve dynamic postural stability, vertical jump and dynamic valgus in female basketball players? METHODS: A hundred and thirteen female basketball players that play in professional clubs were recruited, reaching the final stage 92 (46 per group). One group (CG) received conventional injury prevention training while the experimental group (EG) added to the conventional team prevention program, a gluteus maximus strength programme of 5 months composed of 4 exercises/2 days per week/2 sets of 10 repetitions per leg. RESULTS: The total injury incidence decreased from 0.33 to 0.16 cases (control group pre=0.43 to post=0.14 cases, EG pre=022 to post=0.19). The EG improved overall (p = 0.000), posterior (p = 0.001), posteromedial (p = 0.001) and posterolateral (p = 0.000) dynamic stability of the right leg; anterior (p = 0.024), medial (p = 0.07) and posteromedial (p = 0.01) of the left leg. Both groups improved vertical jump (GC: p = 0.045 and GE: p = 0.000). There was no significant improvement in pain or valgus. SIGNIFICANCE: This strength programme is effective in improving dynamic stability especially of the dominant leg and jump height.


Subject(s)
Basketball , Humans , Female , Basketball/injuries , Lower Extremity/physiology , Postural Balance/physiology , Pain , Muscles , Muscle Strength/physiology
4.
J Clin Med ; 12(15)2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37568407

ABSTRACT

Accurately diagnosing specific variants of alopecia remains challenging for pathologists, potentially delaying appropriate therapeutic decisions by dermatologists. Issues such as limited knowledge on optimal biopsy types and processing methods add complexity. Understanding the normal histology of hair follicles and their changes throughout the follicular cycle further complicates microscopic evaluation. This paper aims to summarize these characteristics and highlight essential diagnostic clues for pathologists to confidently suggest a diagnosis, therefore playing a key role in alopecia diagnosis. Ongoing education, collaboration with dermatologists, and staying up to date on advancements is crucial for the accurate diagnosis and effective management of different types of alopecia.

5.
Foods ; 12(9)2023 May 06.
Article in English | MEDLINE | ID: mdl-37174439

ABSTRACT

There is a growing demand for clean-label products. This study aimed to obtain a food-grade coloring ingredient for meat products based on the formation of Zn-protoporphyrin from porcine livers, thus contributing to the development of nitrite-free products. First, the effects of sodium disulfite and acetic, ascorbic, and lactic acids on the formation of Zn-protoporphyrin and the total microbial count were studied. The combination of ascorbic and acetic acids resulted in a higher Zn-protoporphyrin content than acetic acid alone, and microbial levels were maintained (ca. 3 log CFU/mL). Second, a response surface methodology was used to maximize Zn-protoporphyrin while maintaining microbiological food standards. To that end, the effects of pH (4.2-5.4), incubation time (3-30 h), and temperature (25-50 °C) were studied. The selected conditions for Zn-protoporphyrin formation involved anaerobic incubation at pH 4.8 and 45 °C for 24 h. The safety was validated through challenge testing for relevant pathogens (Listeria monocytogenes, Salmonella spp., and Clostridium perfringens). A significant reduction (>6 log units) was observed in the selected conditions for L. monocytogenes and Salmonella, whereas C. perfringens spores remained at the inoculated levels. The optimized procedure is proven to be microbiologically safe, and may improve the color of nitrite-free meat products.

6.
Rev Esp Patol ; 56(1): 69-72, 2023.
Article in Spanish | MEDLINE | ID: mdl-36599602

ABSTRACT

Well Differentiated Papillary Mesothelioma (MPBD) is a very rare neoplasm that mainly affects women of reproductive age. The most common location is the peritoneum and it is an incidental finding, with a generally favorable prognosis. We present three cases diagnosed incidentally, in the course of a surgical intervention of various causes, which presented as peritoneal exophytic lesions not detected in the pre-surgical imaging study. It is important to keep this entity in mind, to differentiate it from other neoplasms with an unfavorable prognosis and evolution, such as Malignant Mesothelioma or primary and metastatic carcinomas. Recent studies give the MPBD a specific immunohistochemical and molecular profile that allow a greater diagnostic precision of the entity.


Subject(s)
Carcinoma , Mesothelioma , Peritoneal Neoplasms , Humans , Female , Peritoneal Neoplasms/pathology , Mesothelioma/diagnosis , Mesothelioma/pathology , Mesothelioma/surgery , Peritoneum/pathology , Prognosis , Carcinoma/pathology
7.
Rev. esp. patol ; 56(1): 69-72, Ene-Mar. 2023. ilus
Article in Spanish | IBECS | ID: ibc-214178

ABSTRACT

El mesotelioma papilar bien diferenciado (MPBD) es una neoplasia muy infrecuente que afecta fundamentalmente a mujeres en edad reproductiva. La localización más habitual es el peritoneo y se trata de un hallazgo incidental, con un pronóstico generalmente favorable. Presentamos tres casos diagnosticados de manera incidental, en el trascurso de una intervención quirúrgica de causas diversas, que se presentaron como lesiones exofíticas peritoneales no detectadas en el estudio de imagen prequirúrgico. Es importante tener presente esta entidad para diferenciarla de otras neoplasias de pronóstico y evolución desfavorable, como el mesotelioma maligno o carcinomas primarios y metastásicos. Estudios recientes le confieren al MPBD un perfil inmunohistoquímico y molecular específico que permiten una mayor precisión diagnóstica de la entidad.(AU)


Well Differentiated Papillary Mesothelioma (MPBD) is a very rare neoplasm that mainly affects women of reproductive age. The most common location is the peritoneum and it is an incidental finding, with a generally favorable prognosis. We present three cases diagnosed incidentally, in the course of a surgical intervention of various causes, which presented as peritoneal exophytic lesions not detected in the pre-surgical imaging study. It is important to keep this entity in mind, to differentiate it from other neoplasms with an unfavorable prognosis and evolution, such as Malignant Mesothelioma or primary and metastatic carcinomas. Recent studies give the MPBD a specific immunohistochemical and molecular profile that allow a greater diagnostic precision of the entity.(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Mesothelioma , Peritoneal Neoplasms , Surgical Procedures, Operative , Inpatients , Physical Examination , Treatment Outcome , Diagnosis, Differential , Pathology, Clinical , Pathology , Spain
9.
Neurosci Biobehav Rev ; 144: 104993, 2023 01.
Article in English | MEDLINE | ID: mdl-36496190

ABSTRACT

Gaze acts from an early age as a cue to orient attention and, thereafter, to infer our social partners' intentions, thoughts, and emotions. Variants of the attentional orienting paradigm have been used to study the orienting capabilities associated to eye gaze. However, to date, it is still unclear whether this methodology truly assesses "social-specific" processes exclusively involved in attention to eye-gaze or the operation of domain-general attentional processes. The present study provides a comprehensive meta-analysis indicating that eye-gaze and non-social directional stimuli, such as arrows, produce equivalent attentional effects. This result casts doubt on the potential utility of the classic cueing task in revealing social-specific processes. On the other hand, we review behavioral evidence suggesting that eye-gaze stimuli may induce higher-order social processes when more specific experimental procedures that analyze qualitative rather than quantitative differences are used. These findings point to an integrated view in which domain-general and social specific processes both contribute to the attentional mechanisms induced by eye-gaze direction. Finally, some proposals about the social components specifically triggered by eye-gaze stimuli are discussed.


Subject(s)
Cues , Fixation, Ocular , Humans , Reaction Time , Emotions
10.
Biomolecules ; 14(1)2023 Dec 31.
Article in English | MEDLINE | ID: mdl-38254657

ABSTRACT

Dietary supplementation with Omega-3 fatty acids seems to promote skeletal health. Therefore, their consumption at imbalanced or excessive levels has offered less beneficial or even prejudicial effects. Fish produced in aquaculture regimes are prone to develop abnormal skeletons. Although larval cultures are usually fed with diets supplemented with Omega-3 Long Chain Polyunsaturated fatty acids (LC-PUFAs), the lack of knowledge about the optimal requirements for fatty acids or about their impact on mechanisms that regulate skeletal development has impeded the design of diets that could improve bone formation during larval stages when the majority of skeletal anomalies appear. In this study, Argyrosomus regius larvae were fed different levels of Omega-3s (2.6% and 3.6% DW on diet) compared to a commercial diet. At 28 days after hatching (DAH), their transcriptomes were analyzed to study the modulation exerted in gene expression dynamics during larval development and identify impacted genes that can contribute to skeletal formation. Mainly, both levels of supplementation modulated bone-cell proliferation, the synthesis of bone components such as the extracellular matrix, and molecules involved in the interaction and signaling between bone components or in important cellular processes. The 2.6% level impacted several genes related to cartilage development, denoting a special impact on endochondral ossification, delaying this process. However, the 3.6% level seemed to accelerate this process by enhancing skeletal development. These results offered important insights into the impact of dietary Omega-3 LC-PUFAs on genes involved in the main molecular mechanism and cellular processes involved in skeletal development.


Subject(s)
Fatty Acids, Omega-3 , Perciformes , Animals , Osteogenesis/genetics , Dietary Supplements , Aquaculture , Cell Proliferation , Fatty Acids, Omega-3/pharmacology , Larva/genetics
12.
Article in English | MEDLINE | ID: mdl-35270490

ABSTRACT

BACKGROUND: We investigated whether individuals with high levels of autistic traits integrate relevant communicative signals, such as facial expression, when decoding eye-gaze direction. METHODS: Students with high vs. low scores on the Autism Spectrum Quotient (AQ) performed a task in which they responded to the eye directions of faces, presented on the left or the right side of a screen, portraying different emotional expressions. RESULTS: In both groups, the identification of gaze direction was faster when the eyes were directed towards the center of the scene. However, in the low AQ group, this effect was larger for happy faces than for neutral faces or faces showing other emotional expressions, whereas participants from high AQ group were not affected by emotional expressions. CONCLUSIONS: These results suggest that individuals with more autistic traits may not integrate multiple communicative signals based on their emotional value.


Subject(s)
Autistic Disorder , Emotions , Eye , Facial Expression , Fixation, Ocular , Humans
13.
Br J Psychol ; 113(3): 718-738, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34997569

ABSTRACT

From early ages, gaze acts as a cue to infer the interests, behaviours, thoughts and emotions of social partners. Despite sharing attentional properties with other non-social directional stimuli, such as arrows, gaze produces unique effects. A spatial interference task revealed this dissociation. The direction of arrows was identified faster on congruent than on incongruent direction-location trials. Conversely, gaze produced a reversed congruency effect (RCE), with faster identifications on incongruent than congruent trials. To determine the emergence of these gaze-specific attentional mechanisms, 214 Spanish children (4-17 years) divided into 6 age groups, performed the aforementioned task across three experiments. Results showed stimulus-specific developmental trajectories. Whereas the standard effect of arrows was unaffected by age, gaze shifted from an arrow-like effect at age 4 to a gaze-specific RCE at age 12. The orienting mechanisms shared by gaze and arrows are already present in 4-year olds and, throughout childhood, gaze becomes a special social cue with additional attentional properties. Besides orienting attention to a direction, as arrows would do, gaze might orient attention towards a specific object that would be attentionally selected. Such additional components may not fully develop until adolescence. Understanding gaze-specific attentional mechanisms may be crucial for children with atypical socio-cognitive development.


Subject(s)
Cues , Fixation, Ocular , Adolescent , Child , Child, Preschool , Humans , Reaction Time/physiology
14.
J Laparoendosc Adv Surg Tech A ; 32(3): 277-281, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33970020

ABSTRACT

Background: Biliary tree cysts (BTCs) represent an either localized or multifocal abnormal dilatation of the biliary tree, which entails an increased risk of acute cholangitis and cholangiocarcinoma (2.5%-16%). Its incidence in Western countries is ∼1/100.000-1/150.000, being more frequent in Asia (1/1.000). These cysts are usually classified according to Todani classification, which is based on site and morphology of cysts. Patients and Methods: This is a retrospective multicentric descriptive study of patients surgically treated for BTCs. From 2005 to 2018, 25 cases were collected between Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) and Ospedale San Paolo (Savona, Italy). Clinical presentation was characterized by abdominal pain, jaundice, fever, and sometimes weight loss. Eight patients presented Todani type I, 1 patient Todani type II, 3 patients Todani III, 1 patient Todani type IV, and 12 patients Todani type V. Results: Among the 25 surgically treated patients, 12 patients underwent liver resection, 7 patients underwent resection of the extrahepatic biliary tree, 3 patients underwent BTC removal through a duodenotomy, 1 patient underwent resection of the extrahepatic biliary tree and liver resection, and 2 patients underwent pancreatoduodenectomy. Overall 30-day morbidity rate was 20%, and 90-day mortality was 0%. Pathologic examination confirmed diagnosis of cholangiocarcinoma in 5 patients (20%). After a median follow-up of 59 months, 20 patients are alive and in good conditions, whereas 50% of patients with cholangiocarcinoma died for disease progression. Conclusions: Surgical treatment for BTCs is associated with acceptable postoperative outcomes, with moderate morbidity and null mortality rates. Moreover, the risk of developing cholangiocarcinoma is still high that prompts surgical treatment once diagnosis is made.


Subject(s)
Bile Duct Neoplasms , Bile Ducts, Extrahepatic , Choledochal Cyst , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Choledochal Cyst/surgery , Hepatectomy , Humans , Retrospective Studies
15.
Transbound Emerg Dis ; 69(5): 3121-3127, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34812592

ABSTRACT

West Nile Virus (WNV; family Flaviviridae, genus flavivirus) is a zoonotic arbovirus worldwide spread. Its genetic diversity has allowed the definition of at least seven lineages, being lineages 1 and 2 the most widely distributed. Western Mediterranean region has been affected by WNV since decades. In Spain, WNV is actively circulating, provoking annual outbreaks in birds, horses and lately in humans. Lineage 1 is responsible for outbreaks that occurred in central and southern regions, while lineage 2 has been recently described in wild birds in north-eastern part of the country. During 2017 season, a disease outbreak in captive raptors was reported in southern Spain and WNV was isolated from a dead northern goshawk. Full genome sequencing was followed by phylogenetic analyses and analyses of the amino acidic substitutions. This strain, named Spain/2017/NG-b, highly differs from those which have been circulating both in Spain and in the neighbouring Mediterranean countries, constituting a new distinct group, tentatively classified in a newly defined cluster 7 within the WNV clade 1a, supporting a new, independent introduction of the virus in the Western Mediterranean region from an unknown origin. Besides, circumstantial evidence indicates that this emerging WNV strain could be behind the subsequent outbreak occurred nearby in horses. Overall, the reinforcement of surveillance programs, especially in wild birds, is essential to early detect the circulation of WNV and other related flaviviruses that could cause outbreaks in wild or domestic birds, equine and human populations.


Subject(s)
Flavivirus , Horse Diseases , West Nile Fever , West Nile virus , Animals , Animals, Wild , Birds , Horse Diseases/epidemiology , Horses , Humans , Phylogeny , Spain/epidemiology , West Nile Fever/epidemiology , West Nile Fever/veterinary
16.
BMJ Open ; 11(12): e053983, 2021 12 10.
Article in English | MEDLINE | ID: mdl-34893486

ABSTRACT

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Retrospective Studies , Spain/epidemiology
17.
Trials ; 22(1): 739, 2021 Oct 25.
Article in English | MEDLINE | ID: mdl-34696784

ABSTRACT

BACKGROUND: The majority of surgical wounds are closed (for example with sutures or staples) and so heal by primary intention. Where closure is not possible, or the wound subsequently breaks down, wounds may be left to heal from the bottom up (healing by secondary intention). Surgical wound healing by secondary intention (SWHSI) frequently presents a significant management challenge. Additional treatments are often required during the course of healing, and thus a significant financial burden is associated with treating these wounds. Increasingly, negative pressure wound therapy (NPWT) is used in the management of SWHSI. This wound dressing system provides a negative pressure (vacuum) to the wound, removing fluid into a canister, which is believed to be conducive to wound healing. Despite the increasing use of NPWT, there is limited robust evidence for the effectiveness of this device. A well-designed and conducted randomised controlled trial is now required to ascertain if NPWT is a clinically and cost-effective treatment for SWHSI. METHODS: SWHSI-2 is a pragmatic, multi-centre, cross surgical specialty, two arm, parallel group, randomised controlled superiority trial. Adult patients with a SWHSI will be randomised to receive either NPWT or usual care (no NPWT) and will be followed up for 12 months. The primary outcome will be time to healing (defined as full epithelial cover in absence of a scab) in number of days since randomisation. Secondary outcomes will include key clinical events (hospital admission or discharge, treatment status, reoperation, amputation, antibiotic use and death), wound infection, wound pain, health-related quality of life, health utility and resource use. DISCUSSION: Given the increasing use of NPWT, despite limited high-quality supporting evidence, the SWHSI-2 Trial will provide robust evidence on the clinical and cost-effectiveness of NPWT in the management of SWHSI. The SWHSI-2 Trial opened to recruitment in May 2019 and is currently recruiting across 20 participating centres. TRIAL REGISTRATION: ISRCTN 26277546 . Prospectively registered on 25 March 2019.


Subject(s)
Negative-Pressure Wound Therapy , Surgical Wound , Adult , Humans , Intention , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic , Surgical Wound/diagnosis , Surgical Wound/therapy , Surgical Wound Infection , Wound Healing
18.
Biomedicines ; 9(6)2021 May 25.
Article in English | MEDLINE | ID: mdl-34070533

ABSTRACT

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood-brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.

20.
Commun Biol ; 4(1): 478, 2021 04 12.
Article in English | MEDLINE | ID: mdl-33846535

ABSTRACT

Mutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR.


Subject(s)
Pelger-Huet Anomaly/genetics , Receptors, Cytoplasmic and Nuclear/genetics , X Chromosome Inactivation/genetics , Animals , Mice , Mice, Knockout , Phenotype , Receptors, Cytoplasmic and Nuclear/metabolism , Lamin B Receptor
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