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Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.
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Trastornos Relacionados con Cocaína , Cocaína , Fístula Cutánea , Autoinmunidad , Cocaína/efectos adversos , Trastornos Relacionados con Cocaína/complicaciones , Fístula Cutánea/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.
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Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/patología , Adulto , Anciano , Estudios Transversales , Progresión de la Enfermedad , Asimetría Facial/diagnóstico , Asimetría Facial/etiología , Femenino , Oftalmopatía de Graves/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
AIM: Postoperative pain remains a major factor in recovery from colorectal resection. There is increasing interest in opioid-sparing analgesia, and intraperitoneal local anaesthetic (IPLA) has recently been shown to be useful in minor laparoscopic and open colorectal procedures. The aim of this study was to evaluate the impact of IPLA on functional recovery following major laparoscopic surgery. In this controlled trial, mobility, as measured by the De Morton Mobility Index (DEMMI), was used as a surrogate for postoperative functional recovery. METHOD: Patients undergoing laparoscopic colorectal resection were randomized either to continuous ropivacaine (0.2% at 4-6 ml/h) or to saline (0.9%) which were administered via intraperitoneal catheter for 3 days postoperatively. Results were analysed in a double-blind manner. DEMMIs were assessed on postoperative days 1, 2, 3, 7 and 30, and data on pain, opioid consumption, gut and respiratory function, length of stay (LOS) and complications were recorded. RESULTS: Ninety-six patients were recruited. There was no difference in primary outcome (i.e., functional recovery) between IPLA and placebo groups. Opioid consumption and LOS were similar between groups, and no differences were found for any secondary outcome measure. There were no adverse events related to ropivacaine. CONCLUSION: Infusional intraperitoneal local anaesthetic appears to be safe but does not improve functional recovery or analgesic consumption following elective laparoscopic colorectal surgery, in the setting of an established enhanced recovery programme.
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Anestésicos Locales/administración & dosificación , Colectomía/efectos adversos , Laparoscopía/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Proctectomía/efectos adversos , Ropivacaína/administración & dosificación , Anciano , Analgésicos Opioides/uso terapéutico , Colectomía/métodos , Colectomía/rehabilitación , Neoplasias Colorrectales/cirugía , Método Doble Ciego , Recuperación Mejorada Después de la Cirugía , Femenino , Humanos , Infusiones Parenterales , Laparoscopía/rehabilitación , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/etiología , Proctectomía/métodos , Proctectomía/rehabilitación , Resultado del TratamientoRESUMEN
Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present (cal bp), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal bp (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers, perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.
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Cerámica/historia , Culinaria/historia , Animales , Organismos Acuáticos/química , Organismos Acuáticos/aislamiento & purificación , Arqueología , Grasas de la Dieta/análisis , Cromatografía de Gases y Espectrometría de Masas , Groenlandia , Historia Antigua , Japón , Lípidos/análisis , Lípidos/química , Isótopos de Oxígeno , Alimentos Marinos/análisis , Alimentos Marinos/historiaRESUMEN
The Functional Annotation of ANimal Genomes (FAANG) project aims, through a coordinated international effort, to provide high quality functional annotation of animal genomes with an initial focus on farmed and companion animals. A key goal of the initiative is to ensure high quality and rich supporting metadata to describe the project's animals, specimens, cell cultures and experimental assays. By defining rich sample and experimental metadata standards and promoting best practices in data descriptions, deposition and openness, FAANG champions higher quality and reusability of published datasets. FAANG has established a Data Coordination Centre, which sits at the heart of the Metadata and Data Sharing Committee. It continues to evolve the metadata standards, support submissions and, crucially, create powerful and accessible tools to support deposition and validation of metadata. FAANG conforms to the findable, accessible, interoperable, and reusable (FAIR) data principles, with high quality, open access and functionally interlinked data. In addition to data generated by FAANG members and specific FAANG projects, existing datasets that meet the main-or more permissive legacy-standards are incorporated into a central, focused, functional data resource portal for the entire farmed and companion animal community. Through clear and effective metadata standards, validation and conversion software, combined with promotion of best practices in metadata implementation, FAANG aims to maximise effectiveness and inter-comparability of assay data. This supports the community to create a rich genome-to-phenotype resource and promotes continuing improvements in animal data standards as a whole.
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Curaduría de Datos/normas , Genómica , Metadatos/normas , Animales , Ganado , Mascotas , Programas InformáticosRESUMEN
This study investigates the effect of dietary supplementation of a ß-glucanase and ß-xylanase enzyme mix to barley based diets, at two different chemical compositions achieved through different agronomical conditions on growth performance, coefficient of apparent total tract digestibility (CATTD) of nutrients, selected faecal microbial populations and faecal scores in piglets. Sixty-four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one of four dietary treatments (n = 8). The dietary treatments were as follows: (T1) low quality barley diet, (T2) low quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement, (T3) high quality barley diet and (T4) high quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement. Piglets offered the low quality barley-based diet had a higher (p < .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F) ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral detergent fibre (NDF) compared with piglets offered the high quality barley diet. Piglets offered the high quality barley-based diet had reduced faecal scores compared to piglets offered the low quality barley-based diet (2.44 vs. 2.57, SEM 0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs. 10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001) in the faeces of piglets offered the high quality barley-based diet compared to piglets offered the low quality barley-based diet. The inclusion of a ß-glucanase and ß-xylanase enzyme complex had no effect on any variable measured. In conclusion, the higher quality barley-based diet showed beneficial effects on the faecal Lactobacillus spp. population and faecal scores of the piglets; however, the higher level of ß-glucans in the diet decreased nutrient digestibility and subsequently decreased the performance.
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Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos , Hordeum/química , Porcinos/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , ADN Bacteriano/genética , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Heces/química , Heces/microbiología , Femenino , MasculinoRESUMEN
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca2+ ) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca2+ mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56dim CD16+ NK cells and CD56bright CD16dim/- NK cells. Ca2+ flux and NK cytotoxicity activity was measured under various stimulants, including pregnenolone sulphate (PregS), thapsigargin (TG), 2-aminoethoxydiphenyl borate (2APB) and ionomycin. Unstimulated CD56bright CD16dim/- NK cells showed significantly reduced TRPM3 receptors in CFS/ME compared with healthy controls (HC). Ca2+ flux showed no significant difference between groups. Moreover, PregS-stimulated CD56bright CD16dim/- NK cells showed a significant increase in Ca2+ flux in CFS/ME patients compared with HC. By comparison, unstimulated CD56dim CD16+ NK cells showed no significant difference in both Ca2+ flux and TRPM3 expression. PregS-stimulated CD56dim CD16+ NK cells increased TRPM3 expression significantly in CFS/ME, but this was not associated with a significant increase in Ca2+ flux. Furthermore, TG-stimulated CD56dim CD16+ NK cells increased K562 cell lysis prior to PregS stimulation in CFS/ME patients compared with HC. Differential expression of TRPM3 and Ca2+ flux between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in CFS/ME.
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Síndrome de Fatiga Crónica/genética , Células Asesinas Naturales/fisiología , Canales Catiónicos TRPM/genética , Adulto , Antígeno CD56/metabolismo , Señalización del Calcio , Citotoxicidad Inmunológica , Femenino , Humanos , Células K562 , Masculino , Persona de Mediana Edad , Pregnenolona/metabolismo , Receptores de IgG/metabolismo , Tapsigargina/metabolismoRESUMEN
Metal nanoparticles incorporated at low concentration into epoxy systems enable in situ curing via photothermal heating. In the process of nanoparticle-mediated photothermal heating, light interacts specifically with particles embedded within a liquid or solid material and this energy is transformed into heat, resulting in significant temperature increase local to each particle with minimal warming of surroundings. The ability to use such internal heating to transform the mechanical properties of a material (e.g., from liquid to rigid solid) without application of damaging heat to the surrounding environment represents a powerful tool for a variety of scientific applications, particularly within the biomedical sector. Uniform particle dispersion is achieved by placing the nanoparticles within solvent miscible with the desired epoxy resin, demonstrating a strategy utilizable for a wide range of materials without requiring chemical modification of the particles or epoxy. Mechanical and thermal properties (storage modulus, T g, and degradation behavior) of the cured epoxy are equivalent to those obtained under traditional heating methods. Selective curing of a shape is demonstrated within a liquid bath of epoxy, where the solid form is generated by rastering a spatially confined, photothermal-driving light beam. The non-irradiated regions are largely unaffected and the solid part is easily removed from the remaining liquid. Temperature profiles showing minimal heating outside the irradiated zone are presented and discussed.
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OBJECTIVE: This proof of principle study evaluated the effectiveness and feasibility of a brief motivational intervention, delivered in mental health in-patient settings, to improve engagement in treatment for drug and alcohol misuse. METHOD: A randomised controlled trial using concealed randomisation, blind, independent assessment of outcome at 3 months. Participants were 59 new adult admissions, to six acute mental health hospital units in one UK mental health service, with schizophrenia related or bipolar disorder diagnoses, users of community mental health services and also misusing alcohol and/or drugs. Participants were randomised to Brief Integrated Motivational Intervention (BIMI) with Treatment As Usual (TAU), or TAU alone. The BIMI took place over a 2-week period and encouraged participants to explore substance use and its impact on mental health. RESULTS: Fifty-nine in-patients (BIMI n = 30; TAU n = 29) were randomised, the BIMI was associated with a 63% relative odds increase in the primary outcome engagement in treatment [OR 1.63 (95% CI 1.01-2.65; P = 0.047)], at 3 months. Qualitative interviews with staff and participants indicated that the BIMI was both feasible and acceptable. CONCLUSION: Mental health hospital admissions present an opportunity for brief motivational interventions focussed on substance misuse and can lead to improvements in engagement.
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Trastorno Bipolar/terapia , Esquizofrenia/terapia , Trastornos Relacionados con Sustancias/terapia , Adulto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Servicios de Salud Mental , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Mal Uso de Medicamentos de Venta con Receta , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.
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Antifúngicos/uso terapéutico , Rechazo de Injerto/epidemiología , Hepatopatías/complicaciones , Trasplante de Hígado/efectos adversos , Micosis/prevención & control , Receptores de Trasplantes , Adulto , Anciano , Algoritmos , Femenino , Estudios de Seguimiento , Rechazo de Injerto/microbiología , Supervivencia de Injerto , Humanos , Huésped Inmunocomprometido , Hepatopatías/microbiología , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Micosis/epidemiología , Micosis/microbiología , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos , Estados Unidos/epidemiologíaRESUMEN
Cytauxzoonosis is a tick-borne disease of felids caused by the protozoan Cytauxzoon felis. This article characterizes the neuropathologic changes in 8 cases of natural C. felis infection in domestic cats with typical clinical signs and pathologic changes in multiple organs. Histologic changes in the brain included intravascular schizont-laden macrophages in leptomeningeal and parenchymal arterioles and venules. Small capillaries throughout the gray and white matter and choroid plexus also appeared occluded. Affected vessels were often surrounded by small to moderate numbers of lymphocytes and plasma cells and multiple areas of hemorrhage. Vasculitis and fibrin thrombi were occasionally present. Parenchymal changes consisted of variable degrees of vacuolation of the gray and white matter, with microgliosis, astrocytosis, astrogliosis, and multiple microhemorrhages. Multiple well-demarcated areas of necrosis observed in 4 cases were characterized by marked vacuolation of the gray or white matter, with necrotic neurons containing shrunken hypereosinophilic cytoplasm and pyknotic nuclei, nuclear debris, swollen axons, and scattered foamy macrophages. The changes in the brains of affected cats were attributed to vascular occlusion and secondary ischemia caused by the protozoal infection.
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Enfermedades de los Gatos/patología , Piroplasmida/aislamiento & purificación , Infecciones Protozoarias en Animales/patología , Animales , Encéfalo/patología , Gatos , Femenino , Isquemia/patología , Isquemia/veterinaria , Masculino , Necrosis/patología , Necrosis/veterinaria , NeuropatologíaRESUMEN
BACKGROUND: Macular edema resulting from central retinal vein occlusion is effectively treated with anti-vascular endothelial growth factor injections. However, some patients need monthly retreatment and still show frequent recurrences. The purpose of this study was to evaluate the visual and anatomic outcomes of refractory macular edema resulting from ischemic central retinal vein occlusion in patients switched from ranibizumab to aflibercept intravitreal injections. PATIENTS AND METHODS: We describe a retrospective series of patients followed in the Medical Retina Unit of the Jules Gonin Eye Hospital for macular edema due to ischemic central retinal vein occlusion, refractory to monthly retreatment with ranibizumab, and changed to aflibercept. Refractory macular edema was defined as persistence of any fluid at each visit one month after last injection during at least 6 months. All patients had to have undergone pan-retinal laser scan. RESULTS: Six patients were identified, one of whom had a very short-term follow-up (excluded from statistics). Mean age was 57±12 years. The mean changes in visual acuity and central macular thickness from baseline to switch were +20.6±20.3 ETDRS letters and -316.4±276.6 µm, respectively. The additional changes from before to after the switch were +9.2±9.5 ETDRS letters and -248.0±248.7 µm, respectively. The injection intervals could often be lengthened after the switch. CONCLUSIONS: Intravitreal aflibercept seems to be a promising alternative treatment for macular edema refractory to ranibizumab in ischemic central retinal vein occlusion.
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Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Ranibizumab/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada/métodos , Femenino , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/efectos de los fármacosRESUMEN
Mast cell tumors are uncommon in horses and typically have a benign clinical course, but there are occasional reports of more aggressive behavior. The objective of this study was to review histologic features and KIT expression patterns of 72 previously diagnosed equine cutaneous mast cell tumors to determine if either is associated with clinical outcomes. Biopsy specimens were reviewed using histologic criteria derived from grading schemes, and KIT antibody expression patterns used in canine tumors and surveys were sent to referring veterinarians for follow-up clinical data. Arabians were overrepresented relative to the reference population. Most tumors were well differentiated with low mitotic rates (96%), and aberrant KIT staining patterns, as described in dogs, were uncommonly identified (12%). Associated clinical disease was uncommon and no tumors exhibited malignant behavior. Overall, KIT staining pattern and histologic features were not associated with poor clinical outcome or abnormal tumor behavior.
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Enfermedades de los Caballos/metabolismo , Enfermedades de los Caballos/patología , Mastocitosis Cutánea/veterinaria , Animales , Caballos , Masculino , Mastocitosis Cutánea/metabolismo , Mastocitosis Cutánea/patología , Clasificación del Tumor/veterinaria , Proteínas Proto-Oncogénicas c-kit/metabolismo , Factores SexualesRESUMEN
INTRODUCTION: The horizontal beam lateral (HBL) position technique for X-ray imaging has been used for nearly a century; however, this can be challenging for the patient and the practitioner, as it potentially compromises patient dignity. This study explores student radiographers' knowledge and experience of lateral hip positions and their impact on diagnostic quality and patient dignity. METHOD: A cross-sectional mixed-method online survey of undergraduate diagnostic radiography students was completed. Likert scale assessments, rank ordering questions, and free-test qualitative responses were utilised for questions on knowledge and experience of different positioning, ease to obtain, patient dignity, diagnostic quality, and need for repeats. Data analysis included descriptive statistics and cross-tabulation non-parametric analysis against variables of age, gender and year of study. RESULTS: Responses were received by n = 42/158 students, a response rate of 27%. The HBL position was the most commonly repeated image (76.6%); the qualitative themes included HBL image quality issues and difficulty in the HBL positioning for elderly or frail patients, often in discomfort and pain. Analysis of student responses to perceived patient dignity in positioning identified 73.8% found the HBL undignified, and 85.7% agreed the Clements-Nakayama (CN) position would be more dignified for patients. The diagnostic image quality of the HBL position (64.2%) was compared to the CN alternative axiolateral (66.6%). Comparison of ease of obtaining the correct position for HBL (47.6%) was higher than CN position (28.6%); this could be due to the lack of experience n = 3/42 (7.1%) of this position. CONCLUSION: Overall, student radiographers' experience and knowledge of various lateral hip positions observed in clinical practice was good. The CN position scored high for diagnostic image (66.6%) and dignity for the patient (85.7%), over the often repeated HBL position (76.6%), which scored lower for image quality (64.2%) and dignity (76.6%). IMPLICATIONS FOR PRACTICE: Radiographers should advocate for professional autonomy and explore alternative positioning techniques. Further investigation into the CN position's utilisation, image quality and radiation dose in England is recommended.
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Introduction: Racial/ethnic disparities in maternal mortality rates represent one of the most significant areas of disparities amongst all conventional population perinatal health measures in the U.S. The alarming trends and persistent disparities of outcomes by race/ethnicity and geographic location reinforce the need to focus on ensuring quality and safety of maternity care for all women. Despite complex multilevel factors impacting maternal mortality and morbidity, there are evidence-based interventions that, when facilitated consistently and properly, are known to improve the health of mothers before, during and after pregnancy. The objective of this project is to test implementation of pre-conception counseling with father involvement in community-based settings to improve cardiovascular health outcomes before and during pregnancy in southeastern United States. Methods and Analysis: This study has two components: a comprehensive needs and assets assessment and a small-scale pilot study. We will conduct a community informed needs and assets assessment with our diverse stakeholders to identify opportunities and barriers to preconception counseling as well as develop a stakeholder-informed implementation plan. Next, we will use the implementation plan to pilot preconception counseling with father involvement in community-based settings. Finally, we will critically assess the context, identify potential barriers and facilitators, and iteratively adapt the way preconception counseling can be implemented in diverse settings. Results of this research will support future research focused on identifying barriers and opportunities for scalable and sustainable public health approaches to implementing evidence-based strategies that reduce maternal morbidity and mortality in the southeastern United States' vulnerable communities. Discussion: Findings will demonstrate that preconception counseling can be implemented in community health settings in the southeastern United States. Furthermore, this study will build the capacity of community-based organizations in addressing the preconception health of their clients. We plan for this pilot to inform a larger scaled-up clinical trial across community health settings in multiple southeastern states.
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Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.
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Células Sanguíneas/química , Química Encefálica , ADN/genética , Enfermedad de Huntington/genética , Mosaicismo , Músculos/química , Secuencias Repetitivas de Ácidos Nucleicos , Espermatozoides/química , Vísceras/química , Adulto , Edad de Inicio , Ganglios Basales/química , Niño , Preescolar , ADN/aislamiento & purificación , Femenino , Humanos , Enfermedad de Huntington/epidemiología , Masculino , Persona de Mediana Edad , Proteínas Musculares/genética , Proteínas del Tejido Nervioso/genética , Especificidad de Órganos , Reacción en Cadena de la PolimerasaRESUMEN
Pfeiffer syndrome (PS; McKusick MIM 101,600) is an autosomal dominant craniosynostosis syndrome with characteristic craniofacial anomalies and broad thumbs and big toes. We have previously demonstrated genetic heterogeneity in PS and mapped a gene to chromosome 8 (ref. 3) and a second to chromosome 10 (ref. 4). The gene on chromosome 8 is the fibroblast growth factor receptor 1 (FGFR1) with a common mutation (C755G) predicting a Pro252Arg substitution. The gene on chromosome 10 is FGFR2 with several different mutations causing sporadic and familial PS (Table 1). We report a recurrent single point mutation in the FGFR3 gene, located on chromosome 4p, in ten unrelated families with craniosynostosis syndromes. This mutation (C749G) predicts a Pro250Arg amino acid substitution in the extracellular domain of the FGFR3 protein. Interestingly, this common mutation occurs precisely at the analogous position within the FGFR3 protein as the mutations in FGFR1 (Pro252Arg) and FGFR2 (Pro253Arg) previously reported in Pfeiffer and Apert syndromes, respectively.
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Acrocefalosindactilia/genética , Craneosinostosis/genética , Mutación Puntual/genética , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Factores de Crecimiento de Fibroblastos/genética , Secuencia de Aminoácidos , Disostosis Craneofacial/genética , Análisis Mutacional de ADN , Femenino , Genes Dominantes/genética , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , SíndromeRESUMEN
NHE3 is one of five plasma membrane Na+/H+ exchangers and is encoded by the mouse gene Slc9a3. It is expressed on apical membranes of renal proximal tubule and intestinal epithelial cells and is thought to play a major role in NaCl and HCO3- absorption. As the distribution of NHE3 overlaps with that of the NHE2 isoform in kidney and intestine, the function and relative importance of NHE3 in vivo is unclear. To analyse its physiological functions, we generated mice lacking NHE3 function. Homozygous mutant (Slc9a3-/-) mice survive, but they have slight diarrhoea and blood analysis revealed that they are mildly acidotic. HCO3- and fluid absorption are sharply reduced in proximal convoluted tubules, blood pressure is reduced and there is a severe absorptive defect in the intestine. Thus, compensatory mechanisms must limit gross perturbations of electrolyte and acid-base balance. Plasma aldosterone is increased in NHE3-deficient mice, and expression of both renin and the AE1 (Slc4a1) Cl-/HCO3- exchanger mRNAs are induced in kidney. In the colon, epithelial Na+ channel activity is increased and colonic H+,K+-ATPase mRNA is massively induced. These data show that NHE3 is the major absorptive Na+/H+ exchanger in kidney and intestine, and that lack of the exchanger impairs acid-base balance and Na+-fluid volume homeostasis.
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Intestinos/fisiología , Riñón/fisiología , Intercambiadores de Sodio-Hidrógeno/fisiología , Animales , Bicarbonatos/metabolismo , Eliminación de Gen , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Absorción Intestinal , Ratones , Ratones Noqueados , Cloruro de Sodio/metabolismo , Intercambiador 3 de Sodio-Hidrógeno , Intercambiadores de Sodio-Hidrógeno/genéticaRESUMEN
Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points ⢠Tumour vascular function is key to tumour development and treatment ⢠Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function ⢠Thus DCE-MRI with pharmacokinetic models can assess novel treatments ⢠Many recent developments are advancing the accuracy of and information from DCE-MRI ⢠Establishing common methodology across multiple centres is challenging and requires accepted guidelines.