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1.
Public Health ; 232: 114-120, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38772199

RESUMEN

OBJECTIVE: To set up and evaluate a new surveillance system for severe acute respiratory infection (SARI) in Scotland. STUDY DESIGN: Cross-sectional study and evaluation of surveillance system. METHODS: The SARI case definition comprised patients aged 16 years or over with an acute respiratory illness presentation requiring testing for influenza and SARS-CoV-2 and hospital admission. Data were collected from SARI cases by research nurses in one tertiary teaching hospital using a bespoke data collection tool from November 2021 to May 2022. Descriptive analyses of SARI cases were carried out. The following attributes of the surveillance system were evaluated according to Centers for Disease Control and Prevention (CDC) guidelines: stability, data quality, timeliness, positive predictive value, representativeness, simplicity, acceptability and flexibility. RESULTS: The final surveillance dataset comprised 1163 records, with cases peaking in ISO week 50 (week ending 19/12/2021). The system produced a stable stream of surveillance data, with the proportion of SARI records with sufficient information for effective surveillance increasing from 65.4% during the first month to 87.0% over time. Similarly, the proportion where data collection was completed promptly was low initially, but increased to 50%-65% during later periods. CONCLUSION: SARI surveillance was successfully established in one hospital, but for a national system, additional sentinel hospital sites across Scotland, with flexibility to ensure consistently high data completeness and timeliness are needed. Data collection should be automated where possible, and demands on clinicians minimised. SARI surveillance should be embedded and resourced as part of a national respiratory surveillance strategy.


Asunto(s)
COVID-19 , Centros de Atención Terciaria , Humanos , Escocia/epidemiología , Estudios Transversales , Femenino , COVID-19/epidemiología , Masculino , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , SARS-CoV-2 , Adulto Joven , Gripe Humana/epidemiología , Gripe Humana/diagnóstico , Vigilancia de la Población/métodos
2.
Br J Haematol ; 203(3): 351-352, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37581247

RESUMEN

Venous thromboembolism (VTE) continues to cause significant morbidity and excess mortality in patients with multiple myeloma. The report by Costa and colleagues demonstrates superiority of direct oral anticoagulants over aspirin in terms of VTE prevention, without increased bleeding complications seen. Commentary on: Costa et al. Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis. Br J Haematol 2023;203:395-403.

3.
Appetite ; 188: 106618, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37257508

RESUMEN

Melanocortin and neuropeptide-Y (NPY) are both involved in feeding and energy regulation, and they have opposite effects in the paraventricular nucleus of the hypothalamus (PVN). The present study examined an interaction between melanocortin in the nucleus of the solitary tract (NTS) and NPY in the PVN. Male Sprague-Dawley rats were implanted with cannulae in the injection sites of interest. In Experiment 1, subjects received either the melanocortin 3/4-receptor (MC3/4) antagonist SHU9119 (0, 10, 50 and 100 pmol/0.5 µl) or the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS. Food intake was measured at 1, 2, 4, 6 and 24-h post-injection. Administration of SHU9119 into the NTS significantly and dose-dependently increased food intake at 1, 2, 4, 6 and 6-24-h, and administration of MTII into the NTS significantly and dose-dependently decreased 24-h free feeding. In Experiment 2, subjects received the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS just prior to NPY (0 and 1µg/0.5 µl) in the PVN. PVN injection of NPY stimulated feeding, and administration of MTII (50, 100 and 200 pmol) into the NTS significantly and dose-dependently decreased NPY-induced feeding at 2, 4, 6 and 6-24-h. These data suggest that there could be a neuronal association between melanocortin in the NTS and NPY in the PVN, and that the melanocortin system in the NTS has an antagonistic effect on NPY-induced feeding in the PVN.


Asunto(s)
Neuropéptido Y , Núcleo Solitario , Humanos , Ratas , Animales , Masculino , Neuropéptido Y/farmacología , Ratas Sprague-Dawley , Núcleo Hipotalámico Paraventricular/fisiología , Melanocortinas/farmacología , Ingestión de Alimentos/fisiología
4.
Knee Surg Sports Traumatol Arthrosc ; 31(10): 4099-4108, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37414947

RESUMEN

PURPOSE: Identifying predictive factors for all-cause reoperation after anterior cruciate ligament reconstruction could inform clinical decision making and improve risk mitigation. The primary purposes of this study are to (1) determine the incidence of all-cause reoperation after anterior cruciate ligament reconstruction, (2) identify predictors of reoperation after anterior cruciate ligament reconstruction using machine learning methodology, and (3) compare the predictive capacity of the machine learning methods to that of traditional logistic regression. METHODS: A longitudinal geographical database was utilized to identify patients with a diagnosis of new anterior cruciate ligament injury. Eight machine learning models were appraised on their ability to predict all-cause reoperation after anterior cruciate ligament reconstruction. Model performance was evaluated via area under the receiver operating characteristics curve. To explore modeling interpretability and radiomic feature influence on the predictions, we utilized a game-theory-based method through SHapley Additive exPlanations. RESULTS: A total of 1400 patients underwent anterior cruciate ligament reconstruction with a mean postoperative follow-up of 9 years. Two-hundred and eighteen (16%) patients experienced a reoperation after anterior cruciate ligament reconstruction, of which 6% of these were revision ACL reconstruction. SHapley Additive exPlanations plots identified the following risk factors as predictive for all-cause reoperation: diagnosis of systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher visual analog scale pain score prior to surgery, hamstring autograft, tibial fixation via radial expansion device, younger age at initial injury, and concomitant meniscal repair. Pertinent negatives, when compared to previous studies, included sex and timing of surgery. XGBoost was the best-performing model (area under the receiver operating characteristics curve of 0.77) and outperformed logistic regression in this regard. CONCLUSIONS: All-cause reoperation after anterior cruciate ligament reconstruction occurred at a rate of 16%. Machine learning models outperformed traditional statistics and identified diagnosis of systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher visual analog scale pain score prior to surgery, hamstring autograft, tibial fixation via radial expansion device, younger age at initial injury, and concomitant meniscal repair as predictive risk factors for reoperation. Pertinent negatives, when compared to previous studies, included sex and timing of surgery. These models will allow surgeons to tabulate individualized risk for future reoperation for patients undergoing anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: III.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Humanos , Reoperación , Lesiones del Ligamento Cruzado Anterior/diagnóstico , Lesiones del Ligamento Cruzado Anterior/cirugía , Factores de Riesgo , Rotura/cirugía , Consejo , Dolor/cirugía
5.
J Shoulder Elbow Surg ; 32(3): e85-e93, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36183898

RESUMEN

BACKGROUND: External beam radiation therapy (XRT) is a commonly used therapeutic modality for the treatment of various chest wall and axillary malignancies. Despite the known risk of local soft tissue dysfunction, and possibly compromised bone ingrowth for cementless implants, there remains limited data on the impact of prior XRT in a shoulder arthroplasty (SA) cohort. This study evaluated the outcomes of primary SA in patients with prior XRT compared to a matched cohort (MC). METHODS: Over a 27-year time period (1993-2020), 80 primary SAs (7 hemiarthroplasties [HAs], 29 anatomic total shoulder arthroplasties [aTSAs], and 44 reverse shoulder arthroplasties [rTSAs]) with previous XRT to the upper chest or axillary region and a minimum of 2-year follow-up were included. This cohort was matched (1:2) according to age, sex, body mass index (BMI), implant, and year of surgery with patients who had undergone HA or TSA for osteoarthritis or RSA for cuff tear arthropathy. Clinical outcomes including pain, active shoulder range of motion (ROM), strength, complications, and reoperations inclusive of revision surgery were assessed. RESULTS: The XRT cohort consisted of 71 (88.8%) women with a mean age of 70.9 (range, 43-87) years, BMI of 30.9 ± 7.6, and follow-up period of 6.6 years (range, 2.0-28.2). In these patients, SA led to substantial improvements in pain, ROM, and strength across the entire cohort. When compared to the MC, the XRT group demonstrated a lower final postoperative forward elevation (FE) (111° vs. 126°; P = .013) and less improvements in pain (5.3 vs. 6.2; P = .002), FE (34° vs. 54°; P = .002), and external rotation (13° vs. 24°; P < .001). There were 14 (17.5%) complications and 7 reoperations in the XRT group, with rotator cuff failure after HA or TSA (n = 4 of 36; 11.1%) as the most common complication and no instances of loose humeral components. The XRT group had a higher rate of complications (17.5% vs. 8.1%; P = .03) but not reoperations (8.8% vs. 3.1%; P = .059). When evaluated by implant, rTSA demonstrated the lowest rate of reoperations followed by aTSA and HA (2.3% vs. 10.3% vs. 42.9%; P = .002). CONCLUSIONS: Primary SA is an effective treatment modality for the improvement of pain, motion, and strength in patients with a history of prior XRT. However, when compared to patients without prior XRT, less clinical improvement and a higher rate of postoperative complications were observed.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Hemiartroplastia , Articulación del Hombro , Humanos , Femenino , Anciano , Masculino , Artroplastía de Reemplazo de Hombro/efectos adversos , Articulación del Hombro/cirugía , Estudios Retrospectivos , Estudios de Cohortes , Resultado del Tratamiento , Dolor/etiología , Rango del Movimiento Articular
6.
J Arthroplasty ; 38(10): 2024-2031.e1, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37236288

RESUMEN

BACKGROUND: Automatic methods for labeling and segmenting pelvis structures can improve the efficiency of clinical and research workflows and reduce the variability introduced with manual labeling. The purpose of this study was to develop a single deep learning model to annotate certain anatomical structures and landmarks on antero-posterior (AP) pelvis radiographs. METHODS: A total of 1,100 AP pelvis radiographs were manually annotated by 3 reviewers. These images included a mix of preoperative and postoperative images as well as a mix of AP pelvis and hip images. A convolutional neural network was trained to segment 22 different structures (7 points, 6 lines, and 9 shapes). Dice score, which measures overlap between model output and ground truth, was calculated for the shapes and lines structures. Euclidean distance error was calculated for point structures. RESULTS: Dice score averaged across all images in the test set was 0.88 and 0.80 for the shape and line structures, respectively. For the 7-point structures, average distance between real and automated annotations ranged from 1.9 mm to 5.6 mm, with all averages falling below 3.1 mm except for the structure labeling the center of the sacrococcygeal junction, where performance was low for both human and machine-produced labels. Blinded qualitative evaluation of human and machine produced segmentations did not reveal any drastic decrease in performance of the automatic method. CONCLUSION: We present a deep learning model for automated annotation of pelvis radiographs that flexibly handles a variety of views, contrasts, and operative statuses for 22 structures and landmarks.


Asunto(s)
Aprendizaje Profundo , Humanos , Radiografía , Redes Neurales de la Computación , Pelvis/diagnóstico por imagen , Periodo Posoperatorio
7.
J Arthroplasty ; 38(7S): S2-S10, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36933678

RESUMEN

BACKGROUND: Many risk factors have been described for periprosthetic femur fracture (PPFFx) following total hip arthroplasty (THA), yet a patient-specific risk assessment tool remains elusive. The purpose of this study was to develop a high-dimensional, patient-specific risk-stratification nomogram that allows dynamic risk modification based on operative decisions. METHODS: We evaluated 16,696 primary nononcologic THAs performed between 1998 and 2018. During a mean 6-year follow-up, 558 patients (3.3%) sustained a PPFFx. Patients were characterized by individual natural language processing-assisted chart review on nonmodifiable factors (demographics, THA indication, and comorbidities), and modifiable operative decisions (femoral fixation [cemented/uncemented], surgical approach [direct anterior, lateral, and posterior], and implant type [collared/collarless]). Multivariable Cox regression models and nomograms were developed with PPFFx as a binary outcome at 90 days, 1 year, and 5 years, postoperatively. RESULTS: Patient-specific PPFFx risk based on comorbid profile was wide-ranging from 0.4-18% at 90 days, 0.4%-20% at 1 year, and 0.5%-25% at 5 years. Among 18 evaluated patient factors, 7 were retained in multivariable analyses. The 4 significant nonmodifiable factors included the following: women (hazard ratio (HR) = 1.6), older age (HR = 1.2 per 10 years), diagnosis of osteoporosis or use of osteoporosis medications (HR = 1.7), and indication for surgery other than osteoarthritis (HR = 2.2 for fracture, HR = 1.8 for inflammatory arthritis, HR = 1.7 for osteonecrosis). The 3 modifiable surgical factors were included as follows: uncemented femoral fixation (HR = 2.5), collarless femoral implants (HR = 1.3), and surgical approach other than direct anterior (lateral HR = 2.9, posterior HR = 1.9). CONCLUSION: This patient-specific PPFFx risk calculator demonstrated a wide-ranging risk based on comorbid profile and enables surgeons to quantify risk mitigation based on operative decisions. LEVEL OF EVIDENCE: Level III, Prognostic.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Distinciones y Premios , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Femenino , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Prótesis de Cadera/efectos adversos , Reoperación , Fracturas del Fémur/epidemiología , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , Factores de Riesgo , Estudios Retrospectivos
8.
Proc Biol Sci ; 289(1978): 20220862, 2022 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-35858070

RESUMEN

Understanding the sensory ecology of species is vital if we are to predict how they will function in a changing environment. Visual cues are fundamentally important for many predators when detecting and capturing prey. However, many marine areas have become more turbid through processes influenced by climate change, potentially affecting the ability of marine predators to detect prey. We performed the first study that directly relates a pelagic seabird species's foraging behaviour to oceanic turbidity. We collected biologging data from 79 foraging trips and 5472 dives of a visually dependent, pursuit-diving seabird, the Manx shearwater (Puffinus puffinus). Foraging behaviour was modelled against environmental variables affecting underwater visibility, including water turbidity, cloud cover and solar angle. Shearwaters were more likely to initiate area-restricted search and foraging dives in clearer waters. Underwater visibility also strongly predicted dive rate and depth, suggesting that fine-scale prey capture was constrained by the detectability of prey underwater. Our novel use of dynamic descriptors of underwater visibility suggests that visual cues are vital for underwater foraging. Our data indicate that climate change could negatively impact seabird populations by making prey more difficult to detect, compounded by the widely reported effects of reduced prey populations.


Asunto(s)
Buceo , Animales , Aves , Ecología , Conducta Alimentaria , Conducta Predatoria
9.
J Shoulder Elbow Surg ; 31(4): 847-854, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34592408

RESUMEN

BACKGROUND: Irreparable rotator cuff tears (IRCTs) pose treatment challenges both clinically and financially. As cost-effectiveness initiatives are prioritized, value-based health care delivery models are becoming increasingly common. The purpose of this study was to perform a comprehensive analysis of the cost, complications, and readmission rates of 3 common surgical treatment options for IRCTs: superior capsular reconstruction (SCR), arthroscopically assisted lower trapezius tendon transfer (LTTT), and reverse shoulder arthroplasty (RSA). METHODS: Between 2018 and 2020, 155 patients who underwent shoulder surgery at a single institution for IRCT with minimal to no arthritis were identified. Procedures performed included 20 SCRs, 47 LTTTs, and 88 RSAs. A cost analysis was designed to include a period of 60 days preoperatively, the index surgical hospitalization, and 90 days postoperatively, including costs of any readmission or reoperation. RESULTS: Mean standardized costs were as follows: preoperative evaluation SCR $507, LTTT $507, and RSA $730; index surgical hospitalization SCR $19,675, LTTT $15,722, and RSA $16,077; and postoperative care SCR $655, LTTT $686, and RSA $404. Significant differences were observed in the index surgical costs (P < .001), with SCR incurring an additional average cost of $3953 and $3598 compared with LTTT and RSA, respectively. The 90-day complication, reoperation, and readmission rates were 0%, 0%, and 0% in the SCR group; 2.1%, 0%, and 0% in the LTTT group; and 3.4%, 0%, and 1.1% in the RSA group, respectively. With the numbers available, differences among the 3 surgical procedures with respect to complication (P = .223), reoperation (P = .999), and readmission rates (P = .568) did not reach statistical significance. CONCLUSIONS: The mean standardized costs for the treatment of 3 common IRCT procedures inclusive of 60-day workup and 90-day postoperative recovery were $16,915, $17,210, and $20,837 for LTTT, RSA (average added cost $295), and SCR (average added cost $3922), respectively. This information may provide surgeons and institutions with cost-related information that will become increasingly relevant with the expansion of value-based surgical reimbursements.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Lesiones del Manguito de los Rotadores , Articulación del Hombro , Músculos Superficiales de la Espalda , Artroscopía , Costos y Análisis de Costo , Humanos , Rango del Movimiento Articular , Lesiones del Manguito de los Rotadores/cirugía , Articulación del Hombro/cirugía , Músculos Superficiales de la Espalda/cirugía , Resultado del Tratamiento
10.
Int J Cancer ; 144(1): 150-159, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29992570

RESUMEN

It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial-mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15-3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17-6.86, p < 0.001) were associated with decreased cancer-specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T-cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer-specific survival independent of TNM-stage (HR 4.12 95% CI 2.30-7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/metabolismo , Transición Epitelial-Mesenquimal , Microambiente Tumoral , Anciano , Cadherinas/biosíntesis , Proteínas Portadoras/biosíntesis , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Proteínas de Microfilamentos/biosíntesis , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Transcripción de la Familia Snail/biosíntesis , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/biosíntesis , beta Catenina/biosíntesis
11.
N Z Vet J ; 67(6): 287-294, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31248334

RESUMEN

Aims: To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. Methods: Male lambs aged 10-12 months (n = 43) were assigned to receive ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). Results: In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. Conclusions and clinical relevance: A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.


Asunto(s)
Alimentación Animal , Ataxia/veterinaria , Bromuros/uso terapéutico , Compuestos de Potasio/uso terapéutico , Enfermedades de las Ovejas/prevención & control , Temblor/veterinaria , Alimentación Animal/efectos adversos , Alimentación Animal/análisis , Alimentación Animal/microbiología , Animales , Animales Recién Nacidos , Ataxia/prevención & control , Ergotamina/efectos adversos , Ergotamina/análisis , Alcaloides Indólicos , Lolium/microbiología , Micotoxinas/administración & dosificación , Micotoxinas/efectos adversos , Ovinos , Enfermedades de las Ovejas/inducido químicamente , Temblor/inducido químicamente , Temblor/prevención & control
12.
N Z Vet J ; 66(6): 281-289, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29949720

RESUMEN

AIMS To develop a clinical model of perennial ryegrass toxicosis (PRGT) based on feeding a known dose of lolitrem B and ergotamine, and to produce a consistent clinical presentation for assessment of disease pathophysiology, neurological changes and neurohistopathology. METHODS Male lambs, aged between 10-12 months, were randomly assigned to either Treatment (n=9) or Control (n=9) groups. Lambs in the Treatment group received feed containing a novel endophyte-infested perennial ryegrass seed, commencing on Day 0 of the Feeding phase with a low induction dose, then increasing after 3 days to provide 0.16 mg/kg live bodywight (LBW)/day of lolitrem B and 0.054 mg/kg LBW/day ergotamine. Lambs were examined daily and when defined signs of PRGT were observed they were transferred to the Testing phase. Neurological examinations, assessment of gait, surface electromyography (EMG) and mechanosensory nociceptive threshold testing were carried out and blood samples collected during both phases of the trial, with a full necropsy, histopathological examination and measurement of faecal cortisol metabolites (FCM) performed on Day 2 of the Testing phase. RESULTS Typical clinical signs of PRGT, including ataxia of vestibulocerebellar origin leading to stumbling, were observed in all Treatment lambs. The median interval from the start of the Feeding phase to entry into the Testing phase was 21 (min 18, max 34) days. Histopathological characterisation of neurological lesions included the presence of Purkinje cell vacuolation, pyknotic granular layer neurons and proximal axonal Purkinje cell spheroids. Lesions were most apparent within the vestibulocerebellum. Mean root-mean-square voltages from triceps EMG increased in Treatment lambs between Feeding phase Day 0 and Testing phase Day 2 (p<0.001). Daily water intake during the Testing phase for the Treatment group was less than in Control group lambs (p=0.002), and concentrations of FCM at necropsy were higher in Treatment compared to Control lambs (p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE Lolitrem B and ergotamine dosing in feed on a live weight basis combined with neurological/gait assessment provides an effective model for investigation of PRGT and potential therapeutics. Assessment of gait changes using defined criteria and RMS voltages from EMG appear to be useful tools for the assessment of the severity of neurological changes.


Asunto(s)
Ergotamina/efectos adversos , Alcaloides Indólicos/efectos adversos , Lolium/toxicidad , Micotoxinas/efectos adversos , Enfermedades de las Ovejas/inducido químicamente , Enfermedades de las Ovejas/fisiopatología , Análisis de Varianza , Animales , Autopsia/veterinaria , Modelos Animales de Enfermedad , Electromiografía/veterinaria , Ergotamina/administración & dosificación , Heces/química , Marcha , Alcaloides Indólicos/administración & dosificación , Masculino , Micotoxinas/administración & dosificación , Nueva Gales del Sur , Distribución Aleatoria , Ovinos
13.
Clin Otolaryngol ; 42(3): 637-650, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27809411

RESUMEN

BACKGROUND: Chronic rhinosinusitis is a very common inflammatory disease that impairs quality of life and is associated with high healthcare spending. Chronic rhinosinusitis treatment commonly involves the use of intranasal corticosteroids, oral antibiotics, and surgery. Macrolides have been identified as a potential treatment option for chronic rhinosinusitis due to their immunomodulatory effects; however, the evidence supporting their use is still conflicting. OBJECTIVE: The purpose of this systematic review was to evaluate new evidence along with previously reported studies of the use of macrolides in the treatment of chronic rhinosinusitis. SEARCH STRATEGY: Medline, EMBASE, Cochrane CENTRAL, LILACS, clinicaltrials.gov, and the International Clinical Trials Registry Platform were all searched (until June 2015 Medline and EMBASE searches were updated January 2016). Randomised controlled trials comparing low-dose macrolide antibiotics versus placebo, as an adjunct to other therapies, or low-dose macrolide therapy alone versus other therapies were included in this review. EVALUATION METHOD: Quality of the evidence was evaluated using the Cochrane risk of bias tool. Continuous outcomes were expressed as mean differences or standardised mean differences with 95% confidence interval. Data were pooled using fixed-effects models. RESULTS: Nine randomised controlled trials met the inclusion criteria. Studies were classified into three distinct comparisons: Low-dose macrolide therapy vs. placebo, low-dose macrolide +/- nasal steroids vs. nasal steroid and low-dose macrolides vs. other therapies. The overall quality of the evidence is low due to limitations in study design, imprecision, and indirectness. CONCLUSIONS: Positive results were seen with the use of macrolide therapy in the postoperative period in patients with nasal polyps. A firm conclusion with respect to the effectiveness of the use of macrolides for the treatment of chronic rhinosinusitis cannot be reached based on the available evidence. Further study using a placebo-controlled design evaluating the use of macrolides in clearly defined chronic rhinosinusitis populations is needed.


Asunto(s)
Antibacterianos/administración & dosificación , Macrólidos/administración & dosificación , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Adulto , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Estudios de Seguimiento , Humanos , Rinitis/complicaciones , Sinusitis/complicaciones , Factores de Tiempo , Resultado del Tratamiento
14.
Pharmacogenomics J ; 16(4): 366-74, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26440730

RESUMEN

The Bicaudal C Homolog 1 (BICC1) gene, which encodes an RNA binding protein, has been identified by genome wide association studies (GWAS) as a candidate gene associated with major depressive disorder (MDD). We explored the hypothesis that MDD associated single-nucleotide polymorphisms (SNPs) affected the ability of cis-regulatory elements within intron 3 of the BICC1 gene to modulate the activity of the BICC1 promoter region. We initially established that the BICC1 promoter drove BICC1 mRNA expression in amygdala, hippocampus and hypothalamus. Intriguingly, we provide evidence that MDD associated polymorphisms alter the ability of the BICC1 promoter to respond to PKA signalling within amygdala neurones. Considering the known role of amygdala PKA pathways in fear learning and mood these observations suggest a possible mechanism through which allelic changes in the regulation of the BICC1 gene in amygdala neurones may contribute to mood disorders. Our findings also suggest a novel direction for the identification of novel drug targets and the design of future personalised therapeutics.The Pharmacogenomics Journal advance online publication, 6 October 2015; doi:10.1038/tpj.2015.62.


Asunto(s)
Amígdala del Cerebelo/metabolismo , Trastorno Depresivo Mayor/genética , Neuronas/metabolismo , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Proteínas de Unión al ARN/genética , Afecto , Amígdala del Cerebelo/fisiopatología , Animales , Sitios de Unión , Células Cultivadas , Biología Computacional , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Activación Enzimática , Humanos , Intrones , Desequilibrio de Ligamiento , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Ratas , Transducción de Señal , Transcripción Genética , Transfección , Regulación hacia Arriba
16.
Adv Physiol Educ ; 40(2): 165-75, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27068991

RESUMEN

The properties of blood and the relative ease of access to which it can be retrieved make it an ideal source to gauge different aspects of homeostasis within an individual, form an accurate diagnosis, and formulate an appropriate treatment regime. Tests used to determine blood parameters such as the erythrocyte sedimentation rate, hemoglobin concentration, hematocrit, bleeding and clotting times, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean cell volume, and determination of blood groups are routinely used clinically, and deviations outside the normal range can indicate a range of conditions such as anemia, pregnancy, dehydration, overhydration, infectious disease, cancer, thyroid disease, and autoimmune conditions, to mention a few. As these tests can be performed relatively inexpensively and do not require high levels of technical expertise, they are ideally suited for use in the teaching laboratory, enabling undergraduate students to link theory to practice. The practicals described here permit students to examine their own blood and that of their peers and compare these with clinically accepted normal ranges. At the end of the practicals, students are required to answer a number of questions about their findings and to link abnormal values to possible pathological conditions by answering a series of questions based on their findings.


Asunto(s)
Fenómenos Fisiológicos Sanguíneos/inmunología , Educación en Salud/métodos , Pruebas Hematológicas/métodos , Aprendizaje Basado en Problemas/métodos , Estudiantes del Área de la Salud , Sangre/inmunología , Sedimentación Sanguínea , Recuento de Eritrocitos/métodos , Índices de Eritrocitos/fisiología , Hematócrito/métodos , Humanos
17.
J Fish Biol ; 88(3): 1088-103, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26817520

RESUMEN

The goal of this study was to compare American eel Anguilla rostrata life history in two inland river systems in Arkansas, U.S.A., that ultimately discharge into the Gulf of Mexico via the Mississippi River and the Red-Atchafalaya catchments. From 21 June 2011 to 24 April 2014, 238 yellow-phase A. rostrata were captured in the middle Ouachita River and tributaries using boat electrofishing and 39 in the lower White River using multiple sampling gears. Most of them were caught downstream of dams in both basins (61%). Medium-sized A. rostrata ranging from 225 to 350 mm total length (LT ) were the most abundant size group in the Ouachita River basin, but they were absent from the White River. Mean LT at age 4 years (i.e. youngest shared age) was 150 mm greater for the White River than the Ouachita River basin. Anguilla rostrata appeared to have a greater initial LT (i.e. minimum size upon arrival) in the White River that allowed them to reach a gonado-somatic index (IG ) of 1·5 up to 4 years earlier, and downstream migration appeared to occur 5 years earlier at 100 mm greater LT ; these differences may be related to increased river fragmentation by dams in the Ouachita River basin. Growth and maturation of A. rostrata in this study were more similar to southern populations along the Atlantic coast than other inland populations. Adult swimbladder nematodes Anguillicoloides crassus were not present in any of the 214 swimbladders inspected. Gulf of Mexico catchments may be valuable production areas for A. rostrata and data from these systems should be considered as range-wide protection and management plans are being developed.


Asunto(s)
Anguilla/anatomía & histología , Anguilla/fisiología , Ríos , Distribución por Edad , Migración Animal , Animales , Arkansas , Tamaño Corporal , Demografía , Golfo de México , México , Razón de Masculinidad , Estados Unidos
18.
Ir Med J ; 108(4): 120-1, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26016306

RESUMEN

Richter's transformation of chronic lymphocytic leukaemia (CLL) to high-grade B-cell Non-Hodgkin lymphoma occurs in < 5% of CLL cases. Transformation of CLL to Hodgkin Lymphoma is a much rarer event and here we describe a patient who developed Richter's transformation into a Hodgkin Lymphoma presenting as rapidly progressive hepatosplenomegaly.


Asunto(s)
Transformación Celular Neoplásica , Enfermedad de Hodgkin/patología , Leucemia Linfocítica Crónica de Células B/patología , Anciano , Hepatomegalia/etiología , Humanos , Masculino , Esplenomegalia/etiología
19.
Environ Sci Technol ; 48(19): 11637-45, 2014 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-25153941

RESUMEN

Hamilton Harbour, Ontario, Canada is one of the most polluted sites on the Great Lakes, and is subject to substantial airborne pollution due to emissions from both heavy industry and intense vehicle traffic. Mutagenic Polycyclic aromatic hydrocarbons (PAHs) are present at very high concentrations in the air and sediment of Hamilton Harbour. We used five variable DNA microsatellites to screen for mutations in 97 families of Double-crested Cormorants (Phalacrocorax auritus) from three wild colonies, two in Hamilton Harbour and one in cleaner northeastern Lake Erie. Mutations were identified in all five microsatellites at low frequencies, with the majority of mutations found in chicks from the Hamilton Harbour site closest to industrial sources of PAH contamination. Microsatellite mutation rates were 6-fold higher at the Hamilton Harbour site closest to the industrial sources of PAH contamination than the other Hamilton Harbour site, and both were higher than the reference colony. A Phase I metabolite of the PAH benzo[a]pyrene identified by LC-MS/MS in bile and liver from Hamilton Harbour cormorant chicks suggests that these cormorants are exposed to and metabolizing PAHs, highlighting their potential to have caused the observed mutations.


Asunto(s)
Contaminantes Atmosféricos/análisis , Aves/genética , Monitoreo del Ambiente/métodos , Repeticiones de Microsatélite , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminación del Aire/efectos adversos , Animales , Benzo(a)pireno/análisis , Análisis Mutacional de ADN , Geografía , Mutágenos , Mutación , Ontario , Espectrometría de Masas en Tándem
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