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Objectives: To investigate the longitudinal trends of decompressive craniectomy (DC) following traumatic brain injury (TBI) or stroke and explore whether the timing of cranial reconstruction affected revision or removal rates using Hospital Episode Statistics (HES) between 2014 and 2019. Design: Retrospective observational cohort study using HES. The time frame definitions mirror those often used in clinical practice. Setting: HES data from neurosurgical centres in England. Participants: HES data related to decompressive craniectomy procedures and cranioplasty following TBI or stroke between 2014 and 2019. Main outcome measures: The primary outcome was the timing and rate of revision/removal compared with cranioplasty within <12 weeks to ≥12 weeks. Results: There were 4627 DC procedures, of which 1847 (40%) were due to head injury, 1116 (24%) were due to stroke, 728 (16%) were due to other cerebrovascular diagnoses, 317 (7%) had mixed diagnosis and 619 (13%) had no pre-specified diagnoses. The number of DC procedures performed per year ranged from 876 in 2014-2015 to 967 in 2018-2019. There were 4466 cranioplasty procedures, with 309 (7%) revisions and/or removals during the first postoperative year. There was a 33% increase in the overall number of cranioplasty procedures performed within 12 weeks, and there were 1823 patients who underwent both craniectomy and cranioplasty during the study period, with 1436 (79%) having a cranioplasty within 1 year. However, relating to the timing of cranial reconstruction, there was no evidence of any difference in the rate of revision or removal surgery in the early timing group (6.5%) compared with standard care (7.9%) (adjusted HR 0.93, 95% CIs 0.61 to 1.43; p=0.75). Conclusions: Overall number of craniectomies and the subsequent requirements for cranioplasty increased steadily during the study period. However, relating to the timing of cranial reconstruction, there was no evidence of an overall difference in the rate of revision or removal surgery in the early timing group.
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Although effective communication is fundamental to nutrition and dietetics practice, providing novice practitioners with efficacious training remains a challenge. Traditionally, human simulated patients have been utilised in health professions training, however their use and development can be cost and time prohibitive. Presented here is a platform the authors have created that allows students to interact with virtual simulated patients to practise and develop their communication skills. Leveraging the structured incorporation of large language models, it is designed by pedagogical content experts and comprises individual cases based on curricula and student needs. It is targeted towards the practice of rapport building, asking of difficult questions, paraphrasing and mistake making, all of which are essential to learning. Students appreciate the individualised and immediate feedback based on validated communication tools that encourage self-reflection and improvement. Early trials have shown students are enthusiastic about this platform, however further investigations are required to determine its impact as an experiential communication skills tool. This platform harnesses the power of artificial intelligence to bridge the gap between theory and practice in communication skills training, requiring significantly reduced costs and resources than traditional simulated patient encounters.
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Dietética , Humanos , Inteligencia Artificial , Escolaridad , Estado Nutricional , ComunicaciónRESUMEN
Background: Alveolar periosteoplasty during primary repair of cleft lip is still a topic of debate due to the fear exacerbating maxillary retrusion. The authors present their experience with early closure of alveolar clefts. The study aims to analyze gingivoperiosteoplasty (GPP) by comparing the use of locoregional flaps versus distant grafts for reconstruction of the lower layer of the primary palate cleft. Methods: Seventeen infants underwent 22 alveolar cleft repairs. After nasal floor repair by nasal mucoperiosteum, the oral layer was repaired by maxillary or gingival periosteal flaps in seven patients with alveolar clefts less than or equal to 6 mm wide, and tibial or pericranial periosteal grafts in 10 patients with wider clefts. At teenage years, crossbites in three flap-GPP and three graft-GPP patients were compared with nine older adolescents without primary GPP. Results: Alveolar clefts were perfectly sealed. Radiographs during the early 3 postoperative years showed new bone formation more posteriorly extended in patients who underwent graft-GPP. Teeth eruption and alveolar rigidity at the mixed dentition age eliminated the need for secondary bone grafting. The anterior crossbites in adolescent patients ranged between -2 and -14 mm; crossing was relatively smaller in patients with a younger age and without cleft palate. The mean crossbite was 7.2 mm in the six teenagers and 9.6 mm in the control cases. Conclusions: Graft-GPP may be a good alternative to flap-GPP, particularly for wide alveolar cleft repair. Maxillary retrusion is aggravated in patients with cleft palate and older age at assessment. GPP may not increase crossbite.
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Phosphate-based glasses (PBG) with appropriate doping agents have been used as solid electrolytes in solid-state ionic devices. Therefore, more light was shed on the electrical, optical, and electrochemical behavior of the phosphate-based glasses (PBG), containing ZnO or CuO in the absence and existence of conductive polyaniline (PANI), since no publications are available concerning this work. The glass samples were prepared by the rapid quenching method, then mixing phosphate glass and polyaniline (PANI) with metal oxide (ZnO, CuO). They were characterized by different techniques; diffuse reflectance spectrophotometer (DRS), broadband dielectric spectrometer (BDS), cyclic voltammetry (CV), and charge-discharge techniques. In the DRS study, the direct and indirect band gap were calculated from Tauc's relationship where CuO-doped glasses have higher values than ZnO-doped glasses. In the BDS study, the permittivity of all glass compositions decreased while AC conductivity increased with increasing frequency. AC conductivity of PBG doped with metal oxides and mixed with PANI exhibited semiconducting features (6.8 × 10-4 S/cm). Further, these composites exhibited lower loss tangent (0.11), and giant permittivity (186,000) compared to the pure PBG. Also, the electrochemical study exhibited that the composite with 7% CuO content has the highest specific capacitance value (82.3 F/g at 1.0 A/g) which increased to about 113% of its first cycle and then decreased to about 55% after 2500 cycles and finally increased again to 77% after 4500 cycles, indicating its good stability. The combination of optical, electrical, and electrochemical features of these composites suggests their use for energy generation and storage devices.
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Background: There is wide-ranging published literature around cranioplasty following traumatic brain injury (TBI) and stroke, but the heterogeneity of outcomes limits the ability for meta-analysis. Consensus on appropriate outcome measures has not been reached, and given the clinical and research interest, a core outcome set (COS) would be beneficial. Objectives: To collate outcomes currently reported across the cranioplasty literature which will subsequently be used in developing a cranioplasty COS. Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All full-text English studies with more than ten patients (prospective) or more than 20 patients (retrospective) published after 1990 examining outcomes in CP were eligible for inclusion. Results: The review included 205 studies from which 202 verbatim outcomes were extracted, grouped into 52 domains, and categorised into one or more of the OMERACT 2.0 framework core area(s). The total numbers of studies that reported outcomes in the core areas are 192 (94%) pathophysiological manifestations/ 114 (56%) resource use/economic impact/ 94 (46%) life impact/mortality 20 (10%). In addition, there are 61 outcome measures used in the 205 studies across all domains. Conclusion: This study shows considerable heterogeneity in the types of outcomes used across the cranioplasty literature, demonstrating the importance and necessity of developing a COS to help standardise reporting across the literature.
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Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative agent of numerous chronic diseases, including caseous lymphadenitis (CLA) in sheep and goats, which has a zoonotic potential in humans in addition to a poor therapeutic response. In this study, out of 120 collected samples, only 12 (10%) were positive for C. pseudotuberculosis by PCR and by intraperitoneal injection of male Guinea pigs and then characterized for antimicrobial susceptibility and its genetic-relatedness by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), which showed 2-4 bands ranging from 100 to 3000 bp that can be clustered into four clusters (C1-C4). Despite the serotype biovar 1 only infecting sheep and goats, ERIC-PCR reveals intra-subtyping variation. Examination of affected LNs and organs revealed marked enlargement with either thick creamy green pus or multiple abscesses of variable sizes with a central caseated core surrounded by dense fibrous capsule. A histopathological examination revealed a central necrotic core surrounded by a peripheral mantle of mononuclear cells and a fibrous capsule. Positive immune expression of nuclear factor kappa B (NF-κB/p65) and interleukin-1ß (IL-1ß) and negative expression of tumor necrosis factor (TNF) in CLA is the first report to our knowledge. Conclusion: In CLA pyogranulomas, IL1ß is a more crucial proinflammatory cytokine than TNF in the regulation of C. pseudotuberculosis infection, which is accompanied by marked NF-κB immunoexpression. Therefore, the NF-κB/p65 signaling pathway is involved in the activation of IL1ß, and additional immunohistochemical studies are required to determine the various roles of NF-κB/p65 in the inflammatory response within CLA pyogranulomas to control this pathogen.
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Background: Obesity is a chronic condition that affects millions globally; consequently, bariatric surgery is the key to this serious issue. Bariatric procedures are rapidly expanding in number and methods to address the recognized problems. So, it would make a sense for surgeons and patients if there is a more physiological bypass surgery technique in Morbid obesity. This study aims to evaluate the outcome proposed technique. Patients and methods: The present study is a retrospective analysis on 256 participants subjected to the proposed bypass procedure from December 1999 to January 2017, the participants were followed up for an interval of 3years. Results: The findings of the present study revealed a significant Excess Weight Loss (EWL). In addition, patients experienced decreased calcium, iron, vitamin B12, Hemoglobin, zinc, and Prothrombin Concentration. However, three to six months after surgery, they experienced a significant improvement until they reached normal levels without any supplement by the end of 12,18 months, with a three-year follow-up. Conclusion: This proposed Bypass Operation aims to adequate digestions as well as selective absorption without inducing any vital deficit. Most of study's population showed no elements inadequacies, although few percentages emerged during the interval of maximal weight reduction, and it were transient and minimal. No minerals or vitamins were needed.
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Decompressive craniectomy (DC) is an operation where a large section of the skull is removed to accommodate brain swelling. Patients who survive will usually require subsequent reconstruction of the skull using either their own bone or an artificial prosthesis, known as cranioplasty. Cranioplasty restores skull integrity but can also improve neurological function. Standard care following DC consists of the performance of cranioplasty several months later as historically, there was a concern that earlier cranioplasty may increase the risk of infection. However, recent systematic reviews have challenged this and have demonstrated that an early cranioplasty (within three months after DC) may enhance neurological recovery. However, patients are often transferred to a rehabilitation unit following their acute index admission and before their cranioplasty. A better understanding of the pathophysiological effects of cranioplasty and the relationship of timing and complications would enable more focused patient tailored rehabilitation programs, thus maximizing the benefit following cranioplasty. This may maximise recovery potential, possibly resulting in improved functional and cognitive gains, enhancement of quality of life and potentially reducing longer-term care needs. This narrative review aims to update multi-disciplinary team regarding cranioplasty, including its history, pathophysiological consequences on recovery, complications, and important clinical considerations both in the acute and rehabilitation settings.
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Pared Abdominal , Hernia Inguinal , Laparoscopía , Hernia Inguinal/cirugía , Herniorrafia/métodos , Humanos , Mallas QuirúrgicasRESUMEN
OBJECTIVES: To evaluate the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) in patients undergoing elective inguinal hernia repair. METHODS: In compliance with PRISMA statement standards, electronic databases were searched to identify all studies reporting the outcomes of TREPP in patients undergoing elective inguinal hernia repair. The outcomes of interest included recurrence, chronic pain, haematoma, and wound infection. Proportion meta-analysis model was constructed to quantify the risk of postoperative complications and direct comparison meta-analysis model was constructed to compare the outcomes of TREPP and other open techniques. Random-effects modelling was applied to calculate pooled outcome data. RESULTS: Seven studies enrolling 1891 patients undergoing TREPP were included. The mean operative time was 26 min (95% CI 15-36). Pooled analyses showed that TREPP was associated with 3.00% (95% CI 1.00-6.00%) risk of recurrence, 3.00% (95% CI 2.00-6.00%) risk of chronic pain, 8.00% (95% CI 0.00-20.00%) risk of haematoma, and 3.00% (95% CI 0.00-6.00%) risk of wound infection. The results remained consistent through subgroup analysis of patients with primary hernias and those with recurrent hernias. Analysis of a limited number of comparative studies showed no difference between TREPP and Lichtenstein technique in terms of recurrence (OR 1.57, P = 0.26) and chronic pain (OR 1.16, P = 0.59). CONCLUSIONS: The best available evidence suggests that TREPP may be a promising technique for elective repair of inguinal hernias as indicated by low risks of recurrence, chronic pain, haematoma, and wound infection. The available evidence is limited to studies from a same country conducted by almost the same research group which may affect generalisability of the findings. Moreover, there is a lack of comparative evidence on outcomes of TREPP versus other techniques highlighting a need for high-quality randomised controlled trials for definite conclusions. Although the available evidence is not adequate for definite conclusions, the results of current study can be used for sample size calculation and power analysis in future trials.
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Dolor Crónico , Hernia Inguinal , Infección de Heridas , Dolor Crónico/etiología , Hematoma/etiología , Hernia Inguinal/complicaciones , Herniorrafia/efectos adversos , Herniorrafia/métodos , Humanos , Dolor Postoperatorio/etiología , Recurrencia , Mallas Quirúrgicas/efectos adversos , Infección de Heridas/complicaciones , Infección de Heridas/cirugíaRESUMEN
BACKGROUND: In mild psoriasis, topical agents remain the mainstay of treatment. However, the available treatments are not satisfactory for a significant proportion of patients in many terms such as efficacy and safety. Because of these deficits, augmentation of therapeutic effect seems desirable. THIS STUDY AIMS: To evaluate the efficacy of topical cyclosporine cream, delivered by fractional CO2 laser vs the efficacy of topical clobetasol cream for the treatment of mild to moderate plaque psoriasis. PATIENTS AND METHODS: Twenty-two patients with chronic plaque psoriasis involving <10% BSA were included in this study. They were randomly allocated into 2 groups. In Group A, patients were instructed to apply cyclosporine cream twice daily for 5 consecutive days per week immediately after fractional carbon dioxide laser session. While in Group B, clobetasol cream was applied twice daily for 5 consecutive days per week until complete clearance or for a maximum of 10 weeks. The efficacy was objectively assisted clinically and by histopathology by using the scores and skin biopsy. RESULTS: There was a significant improvement of erythema, plaque elevation, and scaling (p < 0.001) with the use of topical cyclosporine cream delivered by the aid of fractional CO2 laser, compared to base line. However, the improvement was more significant with topical clobetasol cream. CONCLUSION: Laser-assisted delivery of topical cyclosporine can provide comparable clinical and pathological improvement to that of clobetasol in the psoriatic plaques. These findings were apparent in patients with less widespread disease. However, topical steroid showed more improvement.
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Clobetasol , Ciclosporina , Psoriasis , Dióxido de Carbono , Clobetasol/efectos adversos , Ciclosporina/efectos adversos , Emolientes , Humanos , Láseres de Gas , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The emergence and spread of multidrug-resistant Salmonella enterica (S. enterica) to humans through food of animal origin are considered a major global public health concern. Currently, little is known about the prevalence of important antimicrobial resistance genes in S. enterica from retail food in Africa. Therefore, the screening and characterization of the extended-spectrum ß-lactamase (ESBL) and plasmid-mediated quinolone resistance (PMQR) genes in S. enterica isolated from retail meats and slaughterhouses in Egypt were done by using PCR and DNA sequencing techniques. Twenty-eight out of thirty-four (82.4%) non-duplicate S. enterica isolates showed multidrug-resistance phenotypes to at least three classes of antimicrobials, and fourteen (41.2%) exhibited an ESBL-resistance phenotype and harbored at least one ESBL-encoding gene. The identified ß-lactamase-encoding genes included blaCTX-M-1, blaCTX-M-3, blaCTX-M-13, blaCTX-M-14, blaCTX-M-15, and blaSHV-12 (ESBL types); blaCMY-2 (AmpC type); and blaTEM-1 and blaOXA-1 (narrow-spectrum types). PMQR genes (included qnrA, qnrB, qnrS, and aac(6')-Ib-cr) were identified in 23 (67.6%) isolates. The presence of ESBL- and PMQR-producing S. enterica with a high prevalence rate in retail meats and slaughterhouses is considered a major threat to public health as these strains with resistance genes could be transmitted to humans through the food chain.
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The increase in multidrug-resistant Salmonella enterica and its spread from food to humans are considered a serious public health concern worldwide. Little is currently known about the prevalence of extended-spectrum ß-lactamase (ESBL)-producing S. enterica in fish in Africa. Therefore, this study aimed to investigate the existence of ESBL-producing S. enterica in retail fish in Egypt. In total, 200 fish samples were collected randomly from various retail fish markets in Egypt. S. enterica were detected in 19 (9.5%; 95% CI: 5.8-14.4) of the fish samples analyzed. Of the 19 non-repetitive S. enterica isolates, 18 were serologically categorized into eight S. enterica serovars and a non-typable serovar. All 19 S. enterica isolates (100%) showed multidrug-resistant phenotypes to at least three classes of antimicrobials, and 11 (57.9%) exhibited an ESBL-resistant phenotype and harbored at least one ESBL-encoding gene. The ESBL-producing S. enterica serovars were as follows: Kentucky (3 isolates; 15.8%), Enteritidis (2 isolates; 10.5%), Typhimurium (2 isolates; 10.5%), and 1 isolate (5.3%) each of Infantis, Virchow, Paratyphi B, and Senftenberg. The identified ß-lactamase-encoding genes included ESBL-encoding genes blaCTX-M-3, blaCTX-M-14, blaCTX-M-15, blaSHV-1, blaSHV-2 and blaSHV-12; the AmpC ß-lactamase-encoding gene blaCMY-2; and the narrow-spectrum ß-lactamase-encoding genes blaTEM-1 and blaOXA-1. All S. enterica isolates were negative for carbapenemase-encoding genes. Molecular analysis of plasmid transferability and replicon typing revealed that most plasmids (with ß-lactamase-encoding genes) were transferrable, and the most common incompatibility groups were IncI1, IncA/C, IncHI1, and IncN. To the best of our knowledge, this is the first report for molecular characterization of ESBL-producing S. enterica in fish in Egypt. The occurrence of ESBL-producing S. enterica in retail fish constitutes a potential public health threat with the possibility of transmission of these strains with resistance genes to humans. Such transmission would exacerbate the resistance to an important class of antibiotics commonly used in hospitals to treat typhoid and non-typhoidal Salmonella infections.
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Peces/microbiología , Salmonelosis Animal/microbiología , Salmonella enterica/metabolismo , beta-Lactamasas/metabolismo , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Egipto/epidemiología , Humanos , Plásmidos/genética , Prevalencia , Salud Pública , Salmonelosis Animal/epidemiología , Salmonella enterica/efectos de los fármacos , Salmonella enterica/genética , Salmonella enterica/aislamiento & purificación , beta-Lactamasas/genéticaRESUMEN
Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kß p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kß/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kß pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.
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Antivirales/farmacología , Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , SARS-CoV-2/efectos de los fármacos , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Chlorocebus aethiops , Curcuma/química , Humanos , Interleucina-6/metabolismo , Cinética , Inhibidor NF-kappaB alfa/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Piper nigrum/química , Factor de Necrosis Tumoral alfa/metabolismo , Células VeroRESUMEN
For integrated optical devices and traveling-wave resonators, realistic use of the superior wave-matter interaction offered by plasmonics is impeded by ohmic loss, which increases rapidly with mode volume reduction. In this work, we report composite hybrid plasmonic waveguides (CHPWs) that are not only capable of guiding subwavelength optical mode with long-range propagation but also unrestricted by stringent requirements in structural, material, or modal symmetry. In these asymmetric CHPWs, the versatility afforded by coupling dissimilar plasmonic modes provides improved fabrication tolerance and more degrees of device design optimization. Experimental realization of CHPWs demonstrates propagation loss and mode area of 0.03 dB/µm and 0.002 µm2, corresponding to the smallest combination among long-range plasmonic structures reported to date. CHPW ring resonators with 2.5-µm radius were realized with record Purcell factor compared with existing plasmonic and dielectric resonators of similar radii.
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Previous studies on the immune system of water buffalo (Bubalus bubalis) using cross-reactive monoclonal antibodies (mAbs) revealed significant similarities and differences to the bovine immune system. Herein, we extend these studies and document the pattern of expression of CD14, CD16, CD163 and CD172a on buffalo leukocytes using a set of cross-reactive mAbs that are known to recognize conserved epitopes within orthologous molecules in cattle, sheep and goats. Buffalo leukocytes were isolated and subjected to mAb labelling for flow cytometry. Single color flow cytometry confirmed mAbs recognition of buffalo orthologues of CD14, CD16, CD163 and CD172a, and revealed consistent patterns of expression similar to that reported in other ruminants. Multicolor flow cytometry revealed that buffalo CD14+ monocytes uniquely co-express CD16, CD163 and CD172a, whereas buffalo granulocytes co-express CD16 and CD172a. This study expands mAbs available to define and study the buffalo monocytes, and also extends information available on the unique features of the buffalo immune system.
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Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Búfalos/inmunología , Leucocitos/inmunología , Receptores de Lipopolisacáridos/inmunología , Receptores de Superficie Celular/inmunología , Receptores de IgG/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Antígenos de Diferenciación/inmunología , Citometría de Flujo/veterinaria , Granulocitos/inmunología , Monocitos/inmunologíaRESUMEN
Traumatic brain injury (TBI) is the leading cause of death and disability in young adults in the developed world. The accuracy of early outcome-prediction remains poor even when all known prognostic factors are considered, suggesting important currently unidentified variables. In addition, whilst survival and neurological outcomes have improved markedly with the utilisation of therapies that optimise physiology, no treatments specifically modulate the underlying pathophysiology. The immunological response to TBI represents both a potential contributor to outcome heterogeneity and a therapeutically tractable component of the acute disease process. Furthermore, chronic inflammation has been linked with neurodegeneration, and may mark a bridge between acute brain injury and the subsequent neurodegenerative process seen in a proportion of patients following TBI. Given the complexity of the immune response and its varying functions ranging from repair of injury to bystander damage of healthy tissue, attempts at immunomodulatory intervention must necessarily be highly targeted towards the maladaptive facets of the inflammatory process. In this review we aim to provide an integrated description of the immunological processes triggered by TBI in both humans and animal models, in particular considering the interplay between the innate immune system, danger-associated molecular patterns and loss of self-tolerance leading to adaptive autoimmunity.
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Lesiones Traumáticas del Encéfalo/inmunología , Inmunidad Adaptativa , Alarminas/inmunología , Animales , Astrocitos/inmunología , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/etiología , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/prevención & control , Daño Encefálico Crónico/etiología , Daño Encefálico Crónico/prevención & control , Lesiones Traumáticas del Encéfalo/complicaciones , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Citocinas/inmunología , Humanos , Inmunidad Innata , Inmunomodulación , Subgrupos Linfocitarios/inmunología , Ratones , Ratones Noqueados , Microglía/inmunología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/inmunología , Enfermedades Neurodegenerativas/prevención & control , Neutrófilos/inmunología , Reconocimiento de Normas Patrones Automatizadas , Ratas , Factores de TiempoRESUMEN
Efforts to develop live attenuated vaccines against Mycobacterium avium subspecies paratuberculosis (Map), using indirect methods to screen Map deletion mutants for potential efficacy, have not been successful. A reduction in the capacity to survive in macrophages has not predicted the ability of mutants to survive in vivo. Previous studies for screening of three deletion mutants in cattle and goats revealed one mutant, with a deletion in relA (ΔMap/relA), could not establish a persistent infection. Further studies, using antigen presenting cells (APC), blood dendritic cells and monocyte derived DC, pulsed with ΔMap/relA or a 35 kDa Map membrane protein (MMP) revealed a component of the response to ΔMap/relA was directed towards MMP. As reported herein, we developed a bacterium viability assay and cell culture assays for analysis and evaluation of cytotoxic T cells generated against ΔMap/relA or MMP. Analysis of the effector activity of responding cells revealed the reason ΔMap/relA could not establish a persistent infection was that vaccination elicited development of cytotoxic CD8 T cells (CTL) with the capacity to kill intracellular bacteria. We demonstrated the same CTL response could be elicited with two rounds of antigenic stimulation of APC pulsed with ΔMap/relA or MMP ex vivo. Cytotoxicity was mediated through the perforin granzyme B pathway. Finally, cognate recognition of peptides presented in context of MHC I and II molecules to CD4 and CD8 T cells is required for development of CTL.
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Proteínas Bacterianas/genética , Secuencia de Bases/genética , Proteínas de la Membrana/genética , Mycobacterium avium subsp. paratuberculosis/genética , Eliminación de Secuencia/genética , Linfocitos T Citotóxicos/inmunología , Animales , Proteínas Bacterianas/metabolismo , Bovinos , Masculino , Proteínas de la Membrana/metabolismo , Viabilidad Microbiana , Mycobacterium avium subsp. paratuberculosis/inmunología , Mycobacterium avium subsp. paratuberculosis/metabolismo , Vacunas AtenuadasRESUMEN
BACKGROUND: Missed abortions are a common problem, often caused by thrombophilia in both recurring and non-recurring cases. AIM: To determine whether the presence of a mutation in the methyltetrahydrofolate reductase (Mthfr) gene correlates with missed abortions. PATIENTS AND METHODS: We selected two hundred patients for this study in two groups: the study group, which consisted of one hundred patients with a history of missed abortion; and the control group, which consisted of one hundred patients with no history of missed abortion. RESULTS: Of the 200 patients, mutations in Mthfr were only found in forty-four patients-thirty-four from the study group and ten from the control group. CONCLUSIONS: Mthfr gene mutation is a common cause of both recurring and non-recurring missed abortions.