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1.
Paediatr Anaesth ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38379426

RESUMO

BACKGROUND: The need for dental rehabilitation under general anesthesia is increasing, with varying needs between patients. Mortality has been found to be a rare event in these patients; however other perioperative events can and do occur. Previous studies have established increased incidence of perioperative events with younger, sicker children, and longer anesthetics, however, no studies to date have evaluated if the incidence of perioperative events is more closely associated with one long anesthetic or multiple anesthetics per patient. AIMS: To evaluate the association of perioperative events related to single anesthetic duration or number of anesthetics per patient for dental rehabilitation. METHODS: After Children's Wisconsin Human Research Protection Program determined this quality activity did not meet the definition of human subjects research, we performed an epidemiologic observational evaluation by extracting all dental related cases (dental alone or with oral surgeon vs. dental with other specialties) with an associated general anesthesia encounter from Children's Wisconsin electronic data warehouse from June 1, 2015 to December 31, 2021. These cases occurred at a free-standing children's hospital or associated pediatric-only ambulatory surgery center. The risk of perioperative safety events was analyzed for previously identified risk groups such as American Society of Anesthesiologists Physical Status (ASA-PS), patient age, anesthesia case time with the addition of number of dental cases per patient. RESULTS: In this study, 8468 procedures were performed on 8082 patients. Of this cohort, 7765 patients underwent one procedure for dental care while 317 patients underwent a total of 703 dental-related procedures, ranging from two to five procedures per patient. Multivariable logistic regression identified increased risk of perioperative events in patients with ASA-PS 3 (n = 1459, rate 1.78%, p value .001, OR 5.7, CI 2.1-15.5) and ASA-PS 4 (n = 86, rate 5.8%, p < .001, OR 17.2, CI 4.4-67.3), anesthesia duration (p < .001, OR 1.46, CI 1.21-1.76), but no increased risk with number of anesthetics per patient (p value .54, OR 0.81, CI 0.4-1.61). CONCLUSIONS: Limiting dental care under general anesthesia to multiple short cases may decrease the risk of perioperative events when compared to completing all treatment in one long operative session.

2.
Sci Rep ; 13(1): 6714, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37185796

RESUMO

Both sharks and humans present a potentially lethal threat to mesopredatory fishes in coral reef systems, with implications for both population dynamics and the role of mesopredatory fishes in reef ecosystems. This study quantifies the antipredator behaviours mesopredatory fishes exhibit towards the presence of large coral reef carnivores and compares these behavioural responses to those elicited by the presence of snorkelers. Here, we used snorkelers and animated life-size models of the blacktip reef shark (Carcharhinus melanopterus) to simulate potential predatory threats to mesopredatory reef fishes (lethrinids, lutjanids, haemulids and serranids). The responses of these reef fishes to the models and the snorkelers were compared to those generated by three non-threatening controls (life-size models of a green turtle [Chelonia mydas], a PVC-pipe [an object control] and a Perspex shape [a second object control]). A Remote Underwater Stereo-Video System (Stereo-RUV) recorded the approach of the different treatments and controls and allowed accurate measurement of Flight Initiation Distance (FID) and categorization of the type of flight response by fishes. We found that mesopredatory reef fishes had greater FIDs in response to the approach of threatening models (1402 ± 402-1533 ± 171 mm; mean ± SE) compared to the controls (706 ± 151-896 ± 8963 mm). There was no significant difference in FID of mesopredatory fishes between the shark model and the snorkeler, suggesting that these treatments provoked similar levels of predator avoidance behaviour. This has implications for researchers monitoring behaviour in situ or using underwater census as a technique to estimate the abundance of reef fishes. Our study suggests that, irrespective of the degree to which sharks actually consume these mesopredatory reef fishes, they still elicit a predictable and consistent antipredator response that has the potential to create risk effects.


Assuntos
Recifes de Corais , Tubarões , Animais , Humanos , Ecossistema , Tubarões/fisiologia , Peixes/fisiologia , Dinâmica Populacional
3.
J Neuromuscul Dis ; 9(5): 655-660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36031906

RESUMO

Limited evidence exists on real-world adherence to nusinersen for the treatment of spinal muscular atrophy (SMA). Data are presented from a multi-site retrospective chart review of 86 adults with SMA initiating nusinersen at nine US centers between January 2017 and February 2019. Seventy-nine (92%) adults remained on nusinersen during the study; 454 (92%) of 493 total nusinersen doses were received on time. Fifty-eight (67%) adults received all nusinersen doses on time. The majority of patients with at least one nonadherent dose resumed nusinersen on time. Most patients followed the dosing schedule across the loading and maintenance dose periods.


Assuntos
Atrofia Muscular Espinal , Adulto , Humanos , Atrofia Muscular Espinal/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , Estudos Retrospectivos
4.
Opt Lett ; 46(10): 2352-2355, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33988581

RESUMO

The backscattered light from agglomerated debris particles shows that an approximate linear correlation exists between the logarithm of the geometric albedo $ \log(A )$ of polydispersions of agglomerated debris particles and their lidar linear or circular depolarization ratios, $ \unicode{x00B5}_L$ and $ \unicode{x00B5}_C$. The nature of the relationship depends on the complex refractive index of the particles in the distribution. This extension of the Umov law can be used for lidar and radar characterizations by placing constraints on the reflectivity of the particles. It suggests that an approximate inverse relationship exists between the lidar ratio and the lidar depolarization ratios whose scaling parameter depends on the refractive index of the aerosol population.

5.
J Equine Vet Sci ; 99: 103425, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33781421

RESUMO

Equine abortions are attributed to both infectious and noninfectious causes. Clinical extrapolations are often made from the experimental model for ascending placentitis towards other causes of fetal compromise, including various markers of inflammation, including the cytokines IL-2, 5, IL-6, IL-10, IFNγ, and TNF. It is unknown if these cytokine changes are noted under field conditions, or if they increase preceding other pregnancy related complications. To assess this, Thoroughbred mares (n = 702) had weekly blood obtained beginning in December 2013 and continuing until parturition. Fetal membranes were submitted to the UKVDL for complete gross and pathologic assessment and classified as either ascending placentitis (n = 6), focal mucoid placentitis (n = 6), idiopathic abortion (n = 6) or control (n = 20). Weekly serum samples were analyzed via immunoassay for concentrations of IL-2, IL-5, IL-6, IL-10, IFNγ, and TNF. For both focal mucoid placentitis and ascending placentitis, an increase (P < .05) in the concentrations of IL-2, IL-5, IL-6, IL-10, IFNγ, and TNF was noted preceding parturition in comparison to controls. Cytokine profiles preceding idiopathic abortion did not differ from controls. In conclusion, serum cytokines may be considered potential biomarkers for the prediction of placental infection, while no changes in cytokine profiles were noted when noninfectious causes of abortion occurred. Additionally, this is the first study to report an increase in cytokines during the disease process of focal mucoid placentitis, the etiology of which includes Nocardioform placentitis.


Assuntos
Doenças dos Cavalos , Doenças Placentárias , Aborto Animal , Animais , Biomarcadores , Citocinas , Feminino , Cavalos , Doenças Placentárias/veterinária , Gravidez
6.
Biol Lett ; 16(11): 20200401, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33202186

RESUMO

Anthropogenic noise is a pollutant of global concern that has been shown to have a wide range of detrimental effects on multiple taxa. However, most noise studies to-date consider only overall population means, ignoring the potential for intraspecific variation in responses. Here, we used field experiments on Australia's Great Barrier Reef to assess condition-dependent responses of blue-green damselfish (Chromis viridis) to real motorboats. Despite finding no effect of motorboats on a physiological measure (opercular beat rate; OBR), we found a condition-dependent effect on anti-predator behaviour. In ambient conditions, startle responses to a looming stimulus were equivalent for relatively poor- and good-condition fish, but when motorboats were passing, poorer-condition fish startled at significantly shorter distances to the looming stimulus than better-condition fish. This greater susceptibility to motorboats in poorer-condition fish may be the result of generally more elevated stress levels, as poorer-condition fish had a higher pre-testing OBR than those in better condition. Considering intraspecific variation in responses is important to avoid misrepresenting potential effects of anthropogenic noise and to ensure the best management and mitigation of this pervasive pollutant.


Assuntos
Peixes , Perciformes , Animais , Ruído/efeitos adversos , Reflexo de Sobressalto
7.
Mol Psychiatry ; 25(5): 918-938, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30862937

RESUMO

The biological fingerprint of environmental adversity may be key to understanding health and disease, as it encompasses the damage induced as well as the compensatory reactions of the organism. Metabolic and hormonal changes may be an informative but incomplete window into the underlying biology. We endeavored to identify objective blood gene expression biomarkers for psychological stress, a subjective sensation with biological roots. To quantify the stress perception at a particular moment in time, we used a simple visual analog scale for life stress in psychiatric patients, a high-risk group. Then, using a stepwise discovery, prioritization, validation, and testing in independent cohort design, we were successful in identifying gene expression biomarkers that were predictive of high-stress states and of future psychiatric hospitalizations related to stress, more so when personalized by gender and diagnosis. One of the top biomarkers that survived discovery, prioritization, validation, and testing was FKBP5, a well-known gene involved in stress response, which serves as a de facto reassuring positive control. We also compared our biomarker findings with telomere length (TL), another well-established biological marker of psychological stress and show that newly identified predictive biomarkers such as NUB1, APOL3, MAD1L1, or NKTR are comparable or better state or trait predictors of stress than TL or FKBP5. Over half of the top predictive biomarkers for stress also had prior evidence of involvement in suicide, and the majority of them had evidence in other psychiatric disorders, providing a molecular underpinning for the effects of stress in those disorders. Some of the biomarkers are targets of existing drugs, of potential utility in patient stratification, and pharmacogenomics approaches. Based on our studies and analyses, the biomarkers with the best overall convergent functional evidence (CFE) for involvement in stress were FKBP5, DDX6, B2M, LAIR1, RTN4, and NUB1. Moreover, the biomarker gene expression signatures yielded leads for possible new drug candidates and natural compounds upon bioinformatics drug repurposing analyses, such as calcium folinate and betulin. Our work may lead to improved diagnosis and treatment for stress disorders such as PTSD, that result in decreased quality of life and adverse outcomes, including addictions, violence, and suicide.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , RNA Helicases DEAD-box/sangue , Proteínas Nogo/sangue , Proteínas Proto-Oncogênicas/sangue , Receptores Imunológicos/sangue , Estresse Psicológico/sangue , Proteínas de Ligação a Tacrolimo/sangue , Microglobulina beta-2/sangue , Adulto , Biomarcadores/sangue , Feminino , Expressão Gênica , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/genética , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Medicina de Precisão , Valor Preditivo dos Testes , Homeostase do Telômero
8.
Cureus ; 11(8): e5404, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31632858

RESUMO

This report discusses a 13-year-old girl diagnosed with beta-propeller protein-associated neurodegeneration (BPAN). BPAN is an X-linked neurodegeneration disorder associated with a mutation in the WDR45 gene. It typically presents in childhood with encephalopathy, developmental delay, and seizures. Following an initial static phase, these symptoms then progress to dementia, dystonia, and parkinsonism in early adulthood. Our child initially presented with epileptic spasms, global developmental delay, speech delay, hypotonia, spasticity, scoliosis, and gait disturbance. While these symptoms remained unchanged in early childhood, they depicted accelerated deterioration at age 12-13 rather than in adulthood. Her diagnosis was made based on her clinical presentation and review of imaging that led to specific genetic testing confirming the condition. The imaging findings were of markedly low signal on gradient T2* sequences in the globus pallidus and substantia nigra and T1 hyperintensity in the substantia nigra, with associated diffuse brain volume loss. Unlike other cases reported in the literature, there was no classic area of central hypointensity on T1 imaging in the substantia nigra.

9.
Ann R Coll Surg Engl ; 101(7): 514-518, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31155899

RESUMO

INTRODUCTION: Mortality rates following hip arthroplasty range between 10% and 40% after 12 months. A higher rate is attributed to postoperative complications, of which surgical site infection is one of the most significant. In an effort to reduce surgical site infection following arthroplasty, antibiotics can be added to the cement used. The primary aim of this study was to determine whether dual antibiotic impregnated cement can reduce the rate of deep surgical site infection in patients following cemented arthroplasty for fractured neck of femur compared with single antibiotic impregnated cement. The secondary aim was to compare the rate of superficial surgical site infection in single compared with dual antibiotic cement. MATERIALS AND METHODS: A total of 206 patients were included. Group 1 included 108 retrospective patients who underwent arthroplasty for neck of femur fracture over a 12-month period using single antibiotic impregnated cement. Group 2 included 98 prospective patients who underwent arthroplasty for neck of femur fracture over a 12-month period using dual antibiotic impregnated cement. The rates of deep and superficial surgical site infection were investigated. RESULTS: Group 1 had a deep surgical site infection rate of 2.9% (n = 3), Group 2 had a deep surgical site infection rate of 0% (n = 0). Group 1 had a superficial surgical site infection rate of 3.7% (n = 4), Group 2 had a superficial surgical site infection rate of 5.1% (n = 5). CONCLUSION: Dual antibiotic cement reduced the rate of deep surgical site infection compared with conventional single antibiotic cement in arthroplasty for fractured neck of femur. Only a marginal difference in superficial surgical site infection was observed.


Assuntos
Antibacterianos/uso terapêutico , Artrite Infecciosa/epidemiologia , Artroplastia de Quadril/efeitos adversos , Cimentos Ósseos/uso terapêutico , Infecções Relacionadas à Prótese/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Artrite Infecciosa/etiologia , Artrite Infecciosa/prevenção & controle , Quimioterapia Combinada/métodos , Feminino , Fraturas do Colo Femoral/mortalidade , Fraturas do Colo Femoral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Taxa de Sobrevida , Resultado do Tratamento
10.
Proc Biol Sci ; 286(1903): 20190562, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31138070

RESUMO

Habitat degradation is a key factor leading to the global loss of biodiversity. This problem is particularly acute in coral reef ecosystems. We investigated whether recognition of predator odours by damselfish was influenced by coral degradation and whether these changes altered survival in the wild. We taught whitespot damselfish to recognize the odour of a predator in the presence of live/healthy coral or dead/degraded coral. Fish were tested for a response to predator odours in environments that matched their conditioning environment or in environments that were mismatched. Next, we taught blue damselfish to recognize the odour of three common reef predators in live and degraded coral environments and then stocked them onto live or degraded patch reefs, where we monitored their subsequent response to predator odour along with their survival. Damselfish learned to recognize predator odours in both coral environments, but the intensity of their antipredator response was much greater when the conditioning and test environments matched. Fish released on degraded coral had about 50% higher survival if they had been trained in the presence of degraded coral rather than live coral. Altering the intensity of antipredator responses could have rather profound consequences on population growth.


Assuntos
Antozoários/química , Peixes/fisiologia , Cadeia Alimentar , Aprendizagem , Longevidade , Odorantes/análise , Animais
11.
Mar Pollut Bull ; 141: 493-500, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955760

RESUMO

Anthropogenic noise can have a negative effect on the physiology and survival of marine fishes. Most research has focused on later life-stages, and few studies have investigated the effects of human-induced noise on embryogenesis. The current study investigated whether playback of motorboat noise affected the embryogenesis of the coral reef damselfishes, Amphiprion melanopus and Acanthochromis polyacanthus. Embryos reared under the playback of boat noise had faster heart rates compared to the ambient reef controls. The effects of noise on morphological development differed between species and the fundamental interrelationships between early life history characteristics changed dramatically under boat noise for Ac. polyacanthus. Noise treatments did not alter the survival rates of embryos under laboratory conditions. Although species specific, our findings suggest that anthropogenic noise causes physiological responses in fishes during embryogenesis and these changes have direct impacts on their development and these alterations may have carry-over effects to later life stages.


Assuntos
Ruído/efeitos adversos , Perciformes/embriologia , Navios , Animais , Beneficência , Recifes de Corais , Gema de Ovo/fisiologia , Feminino , Frequência Cardíaca , Larva , Perciformes/fisiologia , Especificidade da Espécie
12.
Mol Psychiatry ; 24(4): 501-522, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30755720

RESUMO

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic.


Assuntos
Dor/tratamento farmacológico , Dor/genética , Medicina de Precisão/métodos , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores Farmacológicos/sangue , Biologia Computacional/métodos , Proteínas Contráteis/genética , Proteínas Contráteis/metabolismo , Reposicionamento de Medicamentos/métodos , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Transcriptoma/genética
13.
J Therm Biol ; 79: 95-102, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30612692

RESUMO

Increasing temperatures are expected to significantly affect the physiological performance of ectotherms, particularly in tropical locations. The shape of an organism's thermal reaction norm can provide important information on its capacity to persist under climate change scenarios; however, difficulty lies in choosing a measurable trait that best depicts physiological performance. This study investigated the effects of elevated temperatures on processes related to oxygen uptake and delivery, including oxygen consumption, haematology, and tissue health for a low-latitude population of coral reef damselfish. Acanthochromis polyacanthus were collected from the Torres Strait (10°31-46'S, 142°20-35'E) and maintained at current average ocean temperatures (+0 °C; seasonally cycling), + 1.5 °C and + 3 °C higher than present day temperatures for 10 months. Aerobic performance indicated a limit to metabolic function at + 3 °C (33 °C), following an increase in aerobic capacity at + 1.5 °C (31.5 °C). Neither haematological parameters nor gill morphology showed the same improvement in performance at + 1.5 °C. Gill histopathology provided the first indicator of a decline in organism health, which corresponded with mortality observations from previous research. Findings from this study suggest thermal specialisation in this low-latitude population as well as variation in thermal sensitivity, depending on the physiological trait.


Assuntos
Mudança Climática , Recifes de Corais , Peixes/fisiologia , Consumo de Oxigênio , Termotolerância , Animais , Temperatura Alta , Oxigênio/análise , Oxigênio/metabolismo , Água do Mar/química
14.
J Inherit Metab Dis ; 42(2): 264-275, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30689204

RESUMO

Mitochondrial aconitase is the second enzyme in the tricarboxylic acid (TCA) cycle catalyzing the interconversion of citrate into isocitrate and encoded by the nuclear gene ACO2. A homozygous pathogenic variant in the ACO2 gene was initially described in 2012 resulting in a novel disorder termed "infantile cerebellar retinal degeneration" (ICRD, OMIM#614559). Subsequently, additional studies reported patients with pathogenic ACO2 variants, further expanding the genetic and clinical spectrum of this disorder to include milder and later onset manifestations. Here, we report an international multicenter cohort of 16 patients (of whom 7 are newly diagnosed) with biallelic pathogenic variants in ACO2 gene. Most patients present in early infancy with severe truncal hypotonia, truncal ataxia, variable seizures, evolving microcephaly, and ophthalmological abnormalities of which the most dominant are esotropia and optic atrophy with later development of retinal dystrophy. Most patients remain nonambulatory and do no acquire any language, but a subgroup of patients share a more favorable course. Brain magnetic resonance imaging (MRI) is typically normal within the first months but global atrophy gradually develops affecting predominantly the cerebellum. Ten of our patients were homozygous to the previously reported c.336C>G founder mutation while the other six patients were all compound heterozygotes displaying 10 novel mutations of whom 2 were nonsense predicting a deleterious effect on enzyme function. Structural protein modeling predicted significant impairment in aconitase substrate binding in the additional missense mutations. This study provides the most extensive cohort of patients and further delineates the clinical, radiological, biochemical, and molecular features of ACO2 deficiency.


Assuntos
Aconitato Hidratase/deficiência , Doenças Neurodegenerativas/diagnóstico , Atrofia Óptica/diagnóstico , Distrofias Retinianas/diagnóstico , Aconitato Hidratase/genética , Adolescente , Ataxia/genética , Cerebelo/patologia , Criança , Pré-Escolar , Ciclo do Ácido Cítrico , Exoma/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Internacionalidade , Imageamento por Ressonância Magnética , Masculino , Microcefalia/genética , Mutação de Sentido Incorreto , Doenças Neurodegenerativas/genética , Atrofia Óptica/genética , Distrofias Retinianas/genética , Síndrome , Adulto Jovem
15.
Sci Adv ; 5(1): eaau7126, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30662947

RESUMO

During the European Middle Ages, the opening of long-distance Asian trade routes introduced exotic goods, including ultramarine, a brilliant blue pigment produced from lapis lazuli stone mined only in Afghanistan. Rare and as expensive as gold, this pigment transformed the European color palette, but little is known about its early trade or use. Here, we report the discovery of lapis lazuli pigment preserved in the dental calculus of a religious woman in Germany radiocarbon-dated to the 11th or early 12th century. The early use of this pigment by a religious woman challenges widespread assumptions about its limited availability in medieval Europe and the gendered production of illuminated texts.


Assuntos
Silicatos de Alumínio/história , Cálculos Dentários/história , Literatura Medieval/história , Freiras/história , Datação Radiométrica , Restos Mortais , Cor , Feminino , Alemanha , História Medieval , Humanos , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Pinturas , Espectrometria por Raios X , Análise Espectral Raman
16.
Data Brief ; 20: 1620-1628, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30263914

RESUMO

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

17.
Ann Behav Med ; 52(8): 621-632, 2018 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-30010703

RESUMO

Background: Maintaining a healthy lifestyle in adulthood has been shown to significantly reduce cardiovascular disease risk. Increasing evidence suggests that behavioral risk factors for cardiovascular disease are established in childhood; however, limited research has evaluated whether childhood psychological factors play a role. Purpose: To evaluate the association between childhood psychological distress and young to mid adulthood healthy lifestyle. Methods: Using prospective data from the 1958 British Birth Cohort, we assessed whether psychological distress in childhood (captured by internalizing and externalizing symptoms at ages 7, 11, and 16 years) predicted healthy lifestyle at ages 33 (N = 10,748) and 42 (N = 9,581) years. Healthy lifestyle was measured using an index previously demonstrated to predict cardiovascular disease, consisting of five components: absence of smoking, moderate alcohol consumption, regular physical activity, healthy diet, and ideal body weight. Results: Few participants (3.8% at age 33 years and 2.8% at age 42 years) endorsed all five healthy lifestyle components. Linear regression models, adjusting for potential child- and family-level confounders, revealed that higher distress levels in childhood were negatively associated with healthy lifestyle at age 33 years (ß = -0.11, SE = 0.01, p < .001) and 42 years (ß = -0.13, SE = 0.01, p < .001). Higher distress was also associated with significantly lower odds of endorsing each lifestyle component, except physical activity, at both ages. Additional analyses indicated that childhood distress levels were highest among those whose lifestyle scores were low at age 33 and further declined between ages 33 and 42. Conclusions: Psychological distress in childhood may indicate children at risk of less healthy lifestyle practices later in life. Although our findings are preliminary, psychological distress may also provide an important target for public health interventions aimed at preventing cardiovascular disease.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Doenças Cardiovasculares/prevenção & controle , Estilo de Vida Saudável , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos
18.
Mol Genet Metab ; 125(1-2): 127-134, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30055994

RESUMO

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.


Assuntos
Alcaptonúria/tratamento farmacológico , Cicloexanonas/administração & dosagem , Nitrobenzoatos/administração & dosagem , Ocronose/tratamento farmacológico , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Alcaptonúria/epidemiologia , Alcaptonúria/metabolismo , Alcaptonúria/patologia , Progressão da Doença , Feminino , Ácido Homogentísico/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Ocronose/epidemiologia , Ocronose/metabolismo , Ocronose/patologia , Reino Unido
19.
Oecologia ; 188(2): 417-427, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29948313

RESUMO

Predicting multiple predator effects (MPEs) on shared prey remains one of the biggest challenges in ecology. Empirical evidence indicates that interactions among predators can alter predation rates and modify any expected linear effects on prey survival. Knowledge on predator density, identity and life-history traits is expected to help predict the behavioral mechanisms that lead to non-linear changes in predation. Yet, few studies have rigorously examined the effects of predator-predator interactions on prey survival, particularly with marine vertebrate predators. Using an additive-substitutive design, we experimentally paired reef piscivores with different hunting mode [active predator, Pseudochromis fuscus (F); ambush predators, Cephalopholis boenak (B), Epinephelus maculatus (M)] to determine how behavioral interactions modified their combined impacts on damselfish prey. Results showed that behavioral patterns among predators matched those predicted from their hunting mode. However, it was the identity of the predators what determined the strength of any positive or negative interactions, and thus the nature and magnitude of MPEs on prey survival (i.e., risk-enhancing effects: treatments BB, MM and FM; risk-reducing: BM; and linear effects: FF, FB). Given the specificity of predator-predator interactions, none of the predators were fully functionally redundant. Even when two species seemed substitutable (i.e., predators F and M), they led to vastly diverse effects when paired with additional predator species (i.e., B). We concluded that knowledge of the identity of the predator species and the behavioral interactions among them is crucial to successfully predict MPEs in natural systems.


Assuntos
Bass , Cadeia Alimentar , Animais , Ecologia , Comportamento Predatório
20.
Haemophilia ; 24(4): e194-e198, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29578274

RESUMO

INTRODUCTION: Desmopressin is commonly used to reduce bleeding in patients with mucocutaneous bleeding disorders and is available in both intravenous and intranasal forms. Given the variability in response to desmopressin at an individual level, its effectiveness should be assessed with a test dose prior to being advised for use. At this time, no trial has extensively compared the use of intranasal desmopressin to intravenous desmopressin. AIMS: To determine whether both forms of desmopressin are equally effective in yielding a positive response in laboratory assays in paediatric patients with von Willebrand disease or probable von Willebrand disease. METHODS: We evaluated medical record data for 58 patients who underwent desmopressin stimulation testing in our haematology clinic during a 1-year period. Data were collected on demographic information and haematologic laboratory assays prior to desmopressin administration and one hour following desmopressin. RESULTS: There was an absolute increase in von Willebrand antigen to levels appropriate for haemostasis following both forms of desmopressin, although this increase was significantly greater in the intravenous group compared to the intranasal group. There was also a significant absolute increase in Ristocetin Cofactor and Factor VIII levels following desmopressin in both groups. CONCLUSION: Both intravenous and intranasal forms of desmopressin produce a positive response during desmopressin stimulation testing and can be used to identify patients for whom this medication would be effective.


Assuntos
Desamino Arginina Vasopressina/administração & dosagem , Desamino Arginina Vasopressina/uso terapêutico , Administração Intranasal , Administração Intravenosa , Criança , Feminino , Humanos , Masculino , Resultado do Tratamento , Doenças de von Willebrand/tratamento farmacológico
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