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BACKGROUND: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. METHODS: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item 'important'. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. RESULTS: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. CONCLUSION: A VBHC-burns core set was developed, consisting of outcomes and quality indicators that are important to burn patients and burn care professionals. The VBHC-burns core set is now systemically monitored and analysed in Dutch burn care to improve care and patient relevant outcomes. As improving burn care and patient relevant outcomes is important worldwide, the developed VBHC-burns core set could be inspiring for other countries.
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BACKGROUND CONTEXT: Lumbar discectomy is a commonly performed surgery following which surgical site infection (SSI) may occur. Prior literature has suggested that, following SSI related to lumbar fusion, the rate of subsequent lumbar surgeries is increased over prolonged periods of time. This has not been studied specifically for lumbar discectomy. PURPOSE: To define factors associated with SSI following lumbar discectomy and determine if subsequently matched cohorts with and without SSI have differential rates of subsequent lumbar surgery beyond irrigation and debridement (I&Ds) over time. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Adult patients undergoing isolated primary lumbar laminotomy/discectomy were identified from the 2010-2021 M157 PearlDiver database. Exclusion criteria included: age<18 years, preoperative diagnosis of infection, neoplastic, or traumatic diagnoses within 90 days prior to index surgery, additional spinal surgeries on the same day as lumbar discectomy, and not being active in the database for at least 90 days postoperative. From this study population, those who developed SSI were identified based on undergoing I&D within 90 days after surgery. Those with versus without SSI were then matched 1:4 based on age, sex, Elixhauser Comorbidity Index (ECI), and obesity. OUTCOME MEASURES: Following initial I&D, incidence of revision lumbar surgery (revision lumbar discectomy, lumbar laminectomy, lumbar fusion) out to 5 years after lumbar discectomy. METHODS: Following index isolated lumbar discectomy, those with versus without SSI requiring I&D were matched and compared for incidence of secondary surgery in defined time intervals (0-6 months, 6-12 months, 1-2 years, 2-5 years) using multivariable logistic regression, controlling for patient age, sex, ECI, and obesity status. RESULTS: Of 323,025 isolated lumbar discectomy patients, SSI requiring I&D was identified for 583 (0.18%). Multivariable analysis revealed several independent predictors of these SSIs: younger age (odds ratio [OR] 0.85 per decade increase), ECI (OR 1.22 per 2-point increase), and obesity (OR 1.30). Following matching of those with versus without SSI requiring I&D, rates of subsequent surgery beyond I&D were compared. Those with SSI had significantly increased odds of lumbar revision in the first six months (OR 5.26, p<.001), but not 6-12 months (p=.462), 1-2 years (p=.515), or 2-5 years (p=.677). CONCLUSIONS: Overall, SSI requiring I&D is a rare postoperative complication following lumbar discectomy. If occurring, subsequent surgery beyond I&D was higher in the first 6 months, but then not increased at subsequent time points out to five years.
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Discectomía , Vértebras Lumbares , Reoperación , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Discectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Vértebras Lumbares/cirugía , Adulto , Estudios Retrospectivos , Reoperación/estadística & datos numéricos , Anciano , Laminectomía/efectos adversos , Factores de RiesgoRESUMEN
In this systematic review, the perioperative outcomes of total intravenous anesthesia (TIVA) and volatile anesthesia were compared in obese adults (BMI ≥ 30 kg/m²) undergoing elective surgery. The review analyzed data from 12 randomized-controlled trials involving 935 patients, sourced from PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Cochrane, Scopus, and Web of Science databases. The focus was on intraoperative vital signs, emergence time, postoperative nausea and vomiting (PONV), duration of post-anesthesia care unit (PACU) stay, and ICU admission rates. Findings showed that TIVA (using propofol) might reduce PONV, but there were no significant differences in other outcomes compared to volatile anesthesia (with desflurane as the most common agent). The review highlights the need for more research, especially comparing sevoflurane with TIVA, to establish clear clinical guidelines for anesthesia in obese patients.
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Nutritional deficiencies represent a prevalent concern among individuals with obesity, stemming from suboptimal dietary habits, chronic inflammation, and preoperative weight reduction efforts. Bariatric surgical interventions, employing either restrictive, malabsorptive or a combination of the two methods, further compound these deficiencies. Commonly observed nutritional deficits following bariatric surgeries include vitamin B12, vitamin D, thiamine, folate, iron, and protein deficiencies. These deficiencies are further complicated by disparities in healthcare resources and income that distinguish low, medium, and high-income countries. The escalating rates of obesity in low- and medium-income countries are primarily attributed to the increasing availability of cheap, nutritionally depleted, and processed foods, coupled with limited access to healthcare. The provision of bariatric surgical interventions in such regions is hindered by the lack of appropriately trained medical personnel and adequate infrastructure. Additionally, the crucial facets of postoperative care, including diligent follow-up, precise weight loss monitoring, and the administration of appropriate nutritional supplements, often remain lacking. This narrative review provides a comprehensive examination of the prevention and treatment of nutritional deficiencies before and after bariatric surgery in the context of varying healthcare resources and income levels. Bariatric procedures and their global prevalence are discussed, and the prevalence, symptoms, and management strategies of specific nutritional deficiencies are explained. This review also outlines practical strategies for providing more equitable care in low- and medium-income countries.
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BACKGROUND: Hallux rigidus is a degenerative condition affecting the middle age population. It affects patients by limiting their first metatarsophalangeal range of motion (ROM) and also, their shoe wear. The objective of our work was to present an original operative technique which preserves the native joint and improves pain with minimal complications. METHODS: We conducted a retrospective multicenter cohort study of 28 patients (30 feet) suffering from moderate hallux rigidus, operated between October 2010 and October 2017 with at least 48months of follow-up. Clinical and radiological assessments included pre- and postoperative ROM, the American Orthopedic Foot and Ankle Society (AOFAS) score and forefoot radiological evaluation. No patients were lost to follow-up. RESULTS: The mean AOFAS score increased from 59 (range, 51 to 67) preoperatively to 84 (range, 80 to 88) at final follow-up. A total of 37 patients (97%) were satisfied. From a ROM point of view, this remained relatively unchanged between preoperative and postoperative values. CONCLUSION: The percutaneous arthroscopically assisted cheilectomy combined with a percutaneous proximal phalanx osteotomy, significantly improves pain in hallux rigidus with index minus in patients with Coughlin stage I and II after a mean of 4-year follow-up. LEVEL OF EVIDENCE: IV.
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Complex behaviors depend on the coordinated activity of neural ensembles in interconnected brain areas. The behavioral function of such coordination, often measured as co-fluctuations in neural activity across areas, is poorly understood. One hypothesis is that rapidly varying co-fluctuations may be a signature of moment-by-moment task-relevant influences of one area on another. We tested this possibility for error-corrective adaptation of birdsong, a form of motor learning which has been hypothesized to depend on the top-down influence of a higher-order area, LMAN (lateral magnocellular nucleus of the anterior nidopallium), in shaping moment-by-moment output from a primary motor area, RA (robust nucleus of the arcopallium). In paired recordings of LMAN and RA in singing birds, we discovered a neural signature of a top-down influence of LMAN on RA, quantified as an LMAN-leading co-fluctuation in activity between these areas. During learning, this co-fluctuation strengthened in a premotor temporal window linked to the specific movement, sequential context, and acoustic modification associated with learning. Moreover, transient perturbation of LMAN activity specifically within this premotor window caused rapid occlusion of pitch modifications, consistent with LMAN conveying a temporally localized motor-biasing signal. Combined, our results reveal a dynamic top-down influence of LMAN on RA that varies on the rapid timescale of individual movements and is flexibly linked to contexts associated with learning. This finding indicates that inter-area co-fluctuations can be a signature of dynamic top-down influences that support complex behavior and its adaptation.
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Acústica , Aprendizaje , Sesgo , Encéfalo , Ácido Dioctil SulfosuccínicoRESUMEN
To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.
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Neoplasias , Linfocitos T , Animales , Humanos , Antígenos de Neoplasias/metabolismo , Receptores ErbB , Inmunoterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Microambiente Tumoral , Complejo CD3/metabolismoRESUMEN
BACKGROUND: Hallux rigidus is the second most frequent pathology of the first ray. Surgical options for degenerative metatarsophalangeal joint disease are either joint destructive or conservative procedures. The hypothesis was that oblique distal shortening osteotomy of the first metatarsal is an effective conservative technique for the management of stage 1 to 3 hallux rigidus. METHODS: We conducted a retrospective cohort study of 87 feet with Coughlin and Shurnas's stage 1-3 hallux rigidus, operated between 2009 and 2019. The cohort consisted in 72 patients (87 feet) with an average age of 57±9 (30/79) years; 22 of 87 (25.3%) feet had the first metatarsal surgery performed in isolation; 65 of 87 (74.7%) had concomitant forefoot procedures, including 31 of 87 (35.6%) with Akin phalangeal osteotomies and 34 of 87 (39.1%) with Moberg phalangeal osteotomies.We evaluated the American Orthopaedic Foot & Ankle Society (AOFAS) Scale, subjective satisfaction, joint amplitudes, shortening rate, and occurrence of postoperative complications with a mean follow-up of 51 months (16/134). RESULTS: The AOFAS score increased from 54.2±11.3 (25/70) preoperatively to 92.2±7.8 (62/100) postoperatively (P < .001). Patients reported excellent or good outcome in 95.4% of cases. The 40-point self-reported pain subscale score improved from 19.6 (± 10.0) to 37.4 (± 5.4), P < .001.The overall range of motion increased from 61±21 (20/110) degrees to 69±17 (35/120) degrees (P < .001). The mean first metatarsal shortening rate (SRpo) was 9.6%. Neither the Coughlin grade, the metatarsal index, or the SRpo influenced the AOFAS score. At 6-month follow-up, 15 patients had transfer metatarsalgia compared with 5 at last follow-up without requiring another surgical procedure. The risk was not significantly different according to Coughlin's stage, preoperative metatarsal index, or SRpo. CONCLUSION: Oblique distal osteotomy of the first metatarsal for stage 1-3 hallux rigidus, often in combination with other first ray procedures, performed well during our follow-up time period, with a high subjective satisfaction rate and few complications. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
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Hallux Rigidus , Hallux Valgus , Huesos Metatarsianos , Articulación Metatarsofalángica , Anciano , Estudios de Seguimiento , Hallux Rigidus/cirugía , Humanos , Huesos Metatarsianos/cirugía , Articulación Metatarsofalángica/cirugía , Persona de Mediana Edad , Osteotomía/métodos , Satisfacción del Paciente , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: A percutaneous selective flexor digitorum brevis (FDB) tenotomy and a proximal interphalangeal (PIP) joint arthrolysis may correct a lesser claw toe deformity keeping flexor digitorum longus (FDL) and active flexion. Our study aimed to verify if the procedure was effective and reliable and if it respects the surrounding soft tissues. MATERIAL AND METHOD: Twelve cadaveric lateral toes were used. A dissection ensured the integrity of both digital nerves, FDL and flexor pulleys and assessed the section of both FDB slips and PIP arthrolysis. RESULTS: A complete section of the two FDB slips was observed in 4 cases (33%). Arthrolysis was achieved in all cases. Surrounding soft tissues were found intact in all cases. CONCLUSION: This procedure is effective regarding PIP arthrolysis, but a technical improvement is required to achieve a reliable section of both FDB slips. In the hands of an experienced surgeon, it has proven to be safe.
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Síndrome del Dedo del Pie en Martillo , Tenotomía , Síndrome del Dedo del Pie en Martillo/cirugía , Humanos , Músculo Esquelético/cirugía , Transferencia Tendinosa/métodos , Tendones/cirugía , Tenotomía/métodosRESUMEN
The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocalizations. Here, we demonstrate that Bengalese finches (Lonchura striata domestica), which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. 'ab-c' versus 'ab-d') in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech.
Human speech and birdsong share numerous parallels. Both humans and birds learn their vocalizations during critical phases early in life, and both learn by imitating adults. Moreover, both humans and songbirds possess specific circuits in the brain that connect the forebrain to midbrain vocal centers. Humans can flexibly control what they say and how by reordering a fixed set of syllables into endless combinations, an ability critical to human speech and language. Birdsongs also vary depending on their context, and melodies to seduce a mate will be different from aggressive songs to warn other males to stay away. However, so far it was unclear whether songbirds are also capable of modifying songs independent of social or other naturally relevant contexts. To test whether birds can control their songs in a purposeful way, Veit et al. trained adult male Bengalese finches to change the sequence of their songs in response to random colored lights that had no natural meaning to the birds. A specific computer program was used to detect different variations on a theme that the bird naturally produced (for example, "ab-c" versus "ab-d"), and rewarded birds for singing one sequence when the light was yellow, and the other when it was green. Gradually, the finches learned to modify their songs and were able to switch between the appropriate sequences as soon as the light cues changed. This ability persisted for days, even without any further training. This suggests that songbirds can learn to flexibly and purposefully modify the way in which they sequence the notes in their songs, in a manner that parallels how humans control syllable sequencing in speech. Moreover, birds can learn to do this 'on command' in response to an arbitrarily chosen signal, even if it is not something that would impact their song in nature. Songbirds are an important model to study brain circuits involved in vocal learning. They are one of the few animals that, like humans, learn their vocalizations by imitating conspecifics. The finding that they can also flexibly control vocalizations may help shed light on the interactions between cognitive processing and sophisticated vocal learning abilities.
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Encéfalo/fisiología , Señales (Psicología) , Pinzones/fisiología , Aprendizaje , Vocalización Animal , Animales , Masculino , Vías Nerviosas/fisiología , Estimulación Luminosa , Factores de Tiempo , Percepción VisualRESUMEN
OBJECTIVE: To assess overall adrenal mineralocorticoid/glucocorticoid/androgen steroidogenesis in childhood-onset systemic lupus erythematosus (cSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve. METHODS: Fifty-one adult cSLE (ACR criteria) patients and 23 healthy controls were evaluated for adrenal steroidogenesis including mineralocorticoid (progesterone, deoxycorticosterone, aldosterone), glucocorticoid (17-OHprogesterone, 11-desoxycortisol, cortisol), and androgen (dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and dihydrotestosterone) hormones. Ovarian reserve assessment included follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone, ovarian volumes, and antral follicle count. RESULTS: The median of current age [29.11 (19-39.8) vs. 30.8 (19.6-42.1) years, p = 0.502] was similar in adult cSLE and controls. Regarding mineralocorticoid/glucocorticoid, the median of progesterone (p = 0.003), 17-OH progesterone (p < 0.001), and 11-desoxycortisol (p = 0.036) were significantly lower in patients compared to controls. All androgen steroidogenesis hormones were reduced in the former group [dehydroepiandrosterone-sulfate (p < 0.001), androstenedione (p = 0.001), total testosterone (p = 0.005), and dihydrotestosterone (p < 0.001)]. Further comparison of patients with and without current use of prednisone and controls revealed a predominant impact on adrenal glucocorticoid and androgen steroidogenesis with reduced levels of 17-OH progesterone [0.17 (0-0.5) vs. 0.27 (0.1-2.9) vs. 0.33 (0.1-0.8) ng/mL, p < 0.001], dehydroepiandrosterone-sulfate [0.155 (0-0.6) vs. 0.49 (0.1-1.6) vs. 1.11 (0.1-2.6) µg/mL, p < 0.001], androstenedione [0.56 (0.2-4.4) vs. 1.7 (0.5-4.5) vs. 2.33 (0.3-3.8) ng/mL, p < 0.001], total testosterone [12 (12-167) vs. 16 (12-28) vs. (16.5 (0-50) ng/d, p = 0.002], and dihydrotestosterone [92.68 (11.8-198.5) vs. 160.62 (37.9-842.1) vs. 188.3 (71.3-543.9) pg/ml, p < 0.001] in patients under this drug. In addition, patients with this therapy had reduced median ovarian volumes [4.14 (2-12) vs. 7.13 (2-25.7) vs. 5.18 (2.4-17.3) cm3, p = 0.028) that was not associated with cyclophosphamide cumulative dose (p > 0.05). The median prednisone dose was 15/mg/day (2.5-40). CONCLUSIONS: We provided novel evidence that cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. Furthermore, low/moderate prednisone use seems to underlie these abnormalities and may also adversely affect ovarian reserve, independently of immunosuppressants. Key Points ⢠cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. ⢠Low/moderate prednisone use may affect ovarian reserve, independently of immunosuppressants.
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Lupus Eritematoso Sistémico , Reserva Ovárica , Adulto , Hormona Antimülleriana , Estradiol , Femenino , Hormona Folículo Estimulante , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Testosterona , Adulto JovenRESUMEN
BACKGROUND: Intramedullary calcaneal nailing is used to treat displaced intra-articular calcaneal fractures. The main goal of the study was to assess the reduction of tomography and secondary goals were patient functional scores and complication rates. METHODS: The functional outcome and restoration of the radiographic parameters were evaluated post-operatively, at three months, at one year, and at the last follow-up. The morphology of the posterior facet was evaluated post-operatively, at one year and at the last follow-up by CTs. RESULTS: Twenty-six patients were included. The mean follow-up was 2.8 years. The mean AOFAS-AHS was 79 at the last follow-up. The mean calcaneal height index and length rose respectively from 0.44 to 0.86 and 83 to 87 mm, and the width decreased from 50 to 46 mm. CONCLUSION: The radiographic parameters were restored. The AOFAS-AHS was comparable with other series. This study confirms the efficiency of this procedure with lower rate of complications.
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Calcáneo/diagnóstico por imagen , Traumatismos de los Pies/diagnóstico por imagen , Fracturas Óseas/diagnóstico por imagen , Calcáneo/cirugía , Traumatismos de los Pies/cirugía , Fijación Intramedular de Fracturas , Fracturas Óseas/cirugía , Humanos , Fijadores Internos , Periodo Posoperatorio , Tomografía Computarizada por Rayos XRESUMEN
Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of "syllables." We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning.
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Pinzones/fisiología , Aprendizaje/fisiología , Vías Nerviosas/fisiología , Vocalización Animal/fisiología , Animales , Ganglios Basales/efectos de los fármacos , Ganglios Basales/fisiología , Corteza Cerebral/fisiología , Vías Eferentes/fisiología , Agonistas del GABA/farmacología , Generalización Psicológica , Aprendizaje/efectos de los fármacos , Masculino , Muscimol/farmacología , Vías Nerviosas/efectos de los fármacos , Prosencéfalo/fisiología , Refuerzo en Psicología , Vocalización Animal/efectos de los fármacosRESUMEN
Mosquito-transmitted chikungunya virus (CHIKV) is an arthritogenic alphavirus of the Togaviridae family responsible for frequent outbreaks of arthritic disease in humans. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleolus. In encephalitic alphaviruses, nuclear translocation induces host cell transcriptional shutoff; however, the role of capsid protein nucleolar localization in arthritogenic alphaviruses remains unclear. Using recombinant enhanced green fluorescent protein (EGFP)-tagged expression constructs and CHIKV infectious clones, we describe a nucleolar localization sequence (NoLS) in the N-terminal region of capsid protein, previously uncharacterized in CHIKV. Mutation of the NoLS by site-directed mutagenesis reduced efficiency of nuclear import of CHIKV capsid protein. In the virus, mutation of the capsid protein NoLS (CHIKV-NoLS) attenuated replication in mammalian and mosquito cells, producing a small-plaque phenotype. Attenuation of CHIKV-NoLS is likely due to disruption of the viral replication cycle downstream of viral RNA synthesis. In mice, CHIKV-NoLS infection caused no disease signs compared to wild-type CHIKV (CHIKV-WT)-infected mice; lack of disease signs correlated with significantly reduced viremia and decreased expression of proinflammatory factors. Mice immunized with CHIKV-NoLS, challenged with CHIKV-WT at 30 days postimmunization, develop no disease signs and no detectable viremia. Serum from CHIKV-NoLS-immunized mice is able to efficiently neutralize CHIKV infection in vitro Additionally, CHIKV-NoLS-immunized mice challenged with the related alphavirus Ross River virus showed reduced early and peak viremia postchallenge, indicating a cross-protective effect. The high degree of CHIKV-NoLS attenuation may improve CHIKV antiviral and rational vaccine design.IMPORTANCE CHIKV is a mosquito-borne pathogen capable of causing explosive epidemics of incapacitating joint pain affecting millions of people. After a series of major outbreaks over the last 10 years, CHIKV and its mosquito vectors have been able to expand their range extensively, now making CHIKV a human pathogen of global importance. With no licensed vaccine or antiviral therapy for the treatment of CHIKV disease, there is a growing need to understand the molecular determinants of viral pathogenesis. These studies identify a previously uncharacterized nucleolar localization sequence (NoLS) in CHIKV capsid protein, begin a functional analysis of site-directed mutants of the capsid protein NoLS, and examine the effect of the NoLS mutation on CHIKV pathogenesis in vivo and its potential to influence CHIKV vaccine design. A better understanding of the pathobiology of CHIKV disease will aid the development of effective therapeutic strategies.
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Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Fiebre Chikungunya/virología , Virus Chikungunya/clasificación , Virus Chikungunya/genética , Variación Genética , Vacunas Virales/inmunología , Transporte Activo de Núcleo Celular , Animales , Fiebre Chikungunya/patología , Fiebre Chikungunya/prevención & control , Virus Chikungunya/aislamiento & purificación , Análisis Mutacional de ADN , Modelos Animales de Enfermedad , Ratones , Mutagénesis Sitio-Dirigida , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutación , Señales de Clasificación de Proteína , Vacunas Virales/administración & dosificación , Vacunas Virales/genética , VirulenciaRESUMEN
AIMS: The aim of this study was to report a single surgeon series of consecutive patients with moderate hallux valgus managed with a percutaneous extra-articular reverse-L chevron (PERC) osteotomy. PATIENTS AND METHODS: A total of 38 patients underwent 45 procedures. There were 35 women and three men. The mean age of the patients was 48 years (17 to 69). An additional percutaneous Akin osteotomy was performed in 37 feet and percutaneous lateral capsular release was performed in 22 feet. Clinical and radiological assessments included the type of forefoot, range of movement, the American Orthopedic Foot and Ankle (AOFAS) score, a subjective rating and radiological parameters. The mean follow-up was 59.1 months (45.9 to 75.2). No patients were lost to follow-up. RESULTS: The mean AOFAS score increased from 62.5 (30 to 80) pre-operatively to 97.1 (75 to 100) post-operatively. A total of 37 patients (97%) were satisfied. At the last follow up there was a statistically significant decrease in the hallux valgus angle, the intermetatarsal angle and the proximal articular set angle. The range of movement of the first metatarsophalangeal joint improved significantly.. There was more improvement in the range of movement in patients who had fixation of the osteotomy of the proximal phalanx. CONCLUSION: Preliminary results of this percutaneous approach are promising. This technique is reliable and reproducible. Its main asset is that it maintains an excellent range of movement. TAKE HOME MESSAGE: The PERC osteotomy procedure is an effective approach for surgical management of moderate hallux valgus which combines the benefits of percutaneous surgery with the versatility of the chevron osteotomy whilst maintaining excellent first MTPJ range of motion.
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Hallux Valgus/cirugía , Osteotomía/métodos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/patología , Humanos , Masculino , Articulación Metatarsofalángica/fisiopatología , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Osteotomía/efectos adversos , Estudios Prospectivos , Radiografía , Rango del Movimiento Articular , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The Brazilian exportation of pet food has shown high growth rates in the last two years and determination of the exposure degree is one of the most important parameters for the risk assessment of chemical compounds. In this study the exposure degree of dogs to mycotoxins was estimated and acceptable daily intake (ADI) and safe pet dietary level (SPDL) were calculated. Thus the natural occurrence of fumonisins, zearalenone and aflatoxins was evaluated in 100 dry dog feed samples provided by pet owners in Paraná State, Brazil. RESULTS: Despite the high frequency of fumonisins (68%), zearalenone (95%) and aflatoxins (68%) in feed samples, the mean levels detected were low. ADI for fumonisins and zearalenone was 20.0 and 1.00 µg kg(-1) body weight (BW) day(-1) respectively and SPDL for fumonisins was 2000 µg kg(-1) feed. The probable daily intake values (1.83 µg fumonisins, 0.93 µg zearalenone and 0.02 µg aflatoxins kg(-1) BW day(-1) ) were low. CONCLUSION: The exposure degree of dogs could be assumed to be very low. However, the co-occurrence of these three or other mycotoxins, and possible synergic or additive effects, should be taken into account when determining the maximum allowed levels or risk assessment. © 2016 Society of Chemical Industry.
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Alimentación Animal/análisis , Contaminación de Alimentos/análisis , Micotoxinas/análisis , Aflatoxinas/análisis , Aflatoxinas/química , Alimentación Animal/microbiología , Animales , Peso Corporal , Brasil , Dieta , Perros , Femenino , Análisis de los Alimentos , Microbiología de Alimentos , Fumonisinas/análisis , Zearalenona/análisisRESUMEN
Chikungunya virus (CHIKV) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs) previously generated towards the capsid protein (CP) of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1-35 and 140-210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP.
Asunto(s)
Anticuerpos Antivirales/inmunología , Proteínas de la Cápside/inmunología , Virus Chikungunya/inmunología , Epítopos de Linfocito B/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Proteínas de la Cápside/genética , Línea Celular , Virus Chikungunya/genética , Mapeo Epitopo , Epítopos de Linfocito B/genética , Unión ProteicaRESUMEN
BACKGROUND AND PURPOSE: Patients with craniosynostosis syndromes caused by mutations in FGFR-2, FGFR-3, and TWIST1 genes are characterized by having prematurely fused skull sutures and skull base synchondroses, which result in a skull deformity and are accompanied by brain anomalies, including altered white matter microarchitecture. In this study, the reliability and reproducibility of DTI fiber tractography was investigated in these patients. The outcomes were compared with those of controls. MATERIALS AND METHODS: DTI datasets were acquired with a 1.5T MR imaging system with 25 diffusion gradient orientations (voxel size = 1.8 × 1.8 × 3.0 mm(3), b-value = 1000 s/mm(2)). White matter tracts studied included the following: corpus callosum, cingulate gyrus, fornix, corticospinal tracts, and medial cerebellar peduncle. Tract pathways were reconstructed with ExploreDTI in 58 surgically treated patients with craniosynostosis syndromes and 7 controls (age range, 6-18 years). RESULTS: Because of the brain deformity and abnormal ventricular shape and size, DTI fiber tractography was challenging to perform in patients with craniosynostosis syndromes. To provide reliable tracts, we adapted standard tracking protocols. Fractional anisotropy was equal to that in controls (0.44 versus 0.45 ± 0.02, P = .536), whereas mean, axial, and radial diffusivity parameters of the mean white matter were increased in patients with craniosynostosis syndromes (P < .001). No craniosynostosis syndrome-specific difference in DTI properties was seen for any of the fiber tracts studied in this work. CONCLUSIONS: Performing DTI fiber tractography in patients with craniosynostosis syndromes was difficult due to partial volume effects caused by an anisotropic voxel size and deformed brain structures. Although these patients have a normal fiber organization, increased diffusivity parameters suggest abnormal microstructural tissue properties of the investigated white matter tracts.
Asunto(s)
Encefalopatías/etiología , Encefalopatías/patología , Craneosinostosis/complicaciones , Craneosinostosis/patología , Imagen de Difusión Tensora/métodos , Vías Nerviosas/patología , Anisotropía , Encéfalo/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , SíndromeRESUMEN
Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of a sensitive epitope-blocking ELISA (EB-ELISA) capable of specifically detecting anti-chikungunya virus (CHIKV) antibodies in clinical samples. The assay uses a monoclonal antibody (mAb) that binds an epitope on the E2 protein of CHIKV and does not exhibit cross-reactivity to other related alphaviruses. We also demonstrated the use of recombinant CHIK virus-like particles (VLPs) as a safe alternative antigen to infectious virions in the assay. Based on testing of 60 serum samples from patients in the acute or convalescent phase of CHIKV infection, the EB-ELISA provided us with 100% sensitivity, and exhibited 98.5% specificity when Ross River virus (RRV)- or Barmah Forest virus (BFV)-immune serum samples were included. This assay meets the public health demands of a rapid, robust, sensitive and specific, yet simple assay for specifically diagnosing CHIK-infections in humans.
Asunto(s)
Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Fiebre Chikungunya/diagnóstico , Virus Chikungunya/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Epítopos/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Virus Chikungunya/aislamiento & purificación , Humanos , Sensibilidad y Especificidad , Virosomas/genética , Virosomas/inmunologíaRESUMEN
INTRODUCTION: Bunionette consists in a lateral prominence of the head of the fifth metatarsal (M5), inducing a callus. Toe malpositioning determines the varus, supraductus or infraductus form. HYPOTHESIS: A percutaneous method without osteosynthesis was assessed in 38 patients suffering from this pathology. PATIENTS AND METHODS: A continuous single-operator multicenter series operated on between May 2005 and January 2012 was analyzed with mean follow-up of 34 months. The inclusion criterion was bunionette with or without varus deviation. All patients were operated on percutaneously without tourniquet, on a day-care basis. All were clinically assessed, preoperatively and at latest FU, by visual analog pain scale (VAS), AOFAS and Coughlin scores, and callus status. Standard radiological assessment comprised monitoring of intermetatarsal (M4M5) and metatarsophalangeal (M5P1) angles. RESULTS: VAS decreased from 8 (range, 6-9) preoperatively to 0.3 (range, 0-1) out of 10 at follow-up. AOFAS score increased from 58 (range, 52-75) to 97 (range, 80-100) out of 100. According to the Coughlin score, 97.5% of patients were satisfied or very satisfied. Deformity correction was systematic, with disappearance of preoperative callus. M4M5 and M5P1 angles decreased respectively from 10° (range, 6-13°) and 16.2° (range, 8-24°) preoperatively to 5.5° (range, 4-8°) and 4.3° (range, 2-9°). There was 1 case of complex regional pain syndrome and 1 delayed consolidation. DISCUSSION: This procedure appeared reliable for correcting all types of bunionette deformity. Other minimally invasive methods with comparable results use pin fixation. The advantages over conventional techniques are the quality of results, low morbidity and absence of osteosynthesis material. The percutaneous technique should, we believe, be widely adopted in this indication. LEVEL OF EVIDENCE: IV.