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Mycobacterium tuberculosis , Tuberculosis , Femenino , Embarazo , Humanos , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
1. The effect of increasing the dose level of a novel consensus bacterial 6-phytase variant on apparent ileal digestibility (AID) of phosphorus (P), phytic acid (inositol hexa-phosphate, IP6) and ileal IP6 degradation profile was studied in diets containing varying phytate-P (PP) levels.2. Ross 308, one-day-old males (n = 1,800) were allocated to cages (20 birds/cage, six cages/treatment) in a completely randomised design employing a 3 × 5 factorial arrangement (three PP levels: 2.45 (low) 2.95 (medium) and 3.45 g/kg (high); five dose levels of phytase (PhyG): 0, 500, 1,000, 2,000 and 4,000 FTU/kg). Phased diets were based on wheat, corn, soybean meal, rapeseed meal and rice bran (d 0 to 10; 2.60 g/kg digestible P, 7.6 g/kg calcium (Ca); d 11 to 21; 2.10 g/kg digestible P, 6.4 g/kg Ca). Ileal digesta was collected on d 21 for determination of P, IP6 and IP-esters content. Data were analysed by factorial ANOVA; means separation was achieved using Tukey's HSD test.3. Increasing PP reduced AID of IP6 and sum of IP3-6 (%) (P < 0.05) but absolute P-release (g/kg diet) above NC was increased (P < 0.05) at high vs. low PP. Increasing phytase dose exponentially increased (P < 0.001) AID IP6, sum of IP3-6 (%) and digestible IP3-6-P g/kg diet (P < 0.001). AID P was increased but there was an interaction with PP level (P < 0.001). Ileal accumulation of IP5-3-P was universally low with PhyG at ≥1,000 FTU/kg (<0.06 g/100 g DM). At 2,000 and 4,000 FTU/kg, AID IP6 was 97.2, 92.7, 92.6% and 100, 97.2, 97.1%, respectively, at low, medium and high PP. At 2,000 FTU/kg, phytate-P release estimated as the increase (above NC) in ileal digestible sum of IP3-6-P in the diet was 2.26, 2.59 and 3.10 g/kg in low, medium and high PP, respectively.4. The data demonstrated that the novel phytase was effective in breaking down phytate to low IP-esters in diets with varied PP content but the optimal dose level for maximising P-release may differ in diets with varying PP content.
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6-Fitasa , 6-Fitasa/metabolismo , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Calcio de la Dieta/metabolismo , Pollos/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Digestión , Ésteres/farmacología , Masculino , Ácido FíticoRESUMEN
BACKGROUND: Preventing surgical site infections and prosthetic joint infections is crucial for patient safety after total joint arthroplasty. Microbial air contamination has been suggested as a risk factor. Therefore, the ventilation system that will reduce air contamination most effectively in operating theatres (OTs) has been discussed. AIM: To determine whether laminar airflow (LAF) ventilation is superior to turbulent airflow (TAF) ventilation by looking at the colony forming units (cfu) count during live total hip and knee arthroplasties. Furthermore, to explore whether the number of OT personnel, door and cabinet lock openings and technical parameters of the ventilation systems have an impact on the number of cfu. METHODS: Active air sampling and passive sedimented bacterial load were performed in 17 OTs, equipped with either LAF or TAF ventilation, during 51 live surgeries while observations were noted. FINDINGS: LAF OTs reduced cfu counts compared with TAF OTs during live surgery (P<0.001). All LAF OTs provided ultraclean air whereas TAF had nine procedures exceeding the threshold of 10 cfu/m3. Door and cabinet lock openings and number of personnel did not influence the cfu count, while it decreased with increasing volume and total air change per hour (P<0.05). CONCLUSION: All LAF OTs had cfu counts within recommendations and provided lower cfu counts compared with TAF OTs. The number of OT personnel and total openings did not have an influence on cfu counts. Increased volume of the OT and total air change per hour showed a decrease in active cfu counts.
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Microbiología del Aire , Artroplastia de Reemplazo de Rodilla , Carga Bacteriana , Recuento de Colonia Microbiana , Humanos , Quirófanos , Infección de la Herida Quirúrgica , VentilaciónRESUMEN
Objective: To summarize the available literature on in utero exposure to maternal rheumatoid arthritis (RA) and its influence on the risk of neurodevelopmental disorders (NDDs) in offspring.Method: We conducted a systematic literature review and assessed the internal validity of studies with the Newcastle Ottawa Scale tool.Results: Six studies were included. Three reported on autism spectrum disorders; one cohort study indicated a slightly elevated risk, and two case-control studies reported too few cases for risk assessment. Two large cohort studies reported elevated hazard ratios for epilepsy in offspring, in overlapping populations. One study on attention deficit hyperactivity disorder (ADHD) reported higher odds for maternal RA during pregnancy, among children with ADHD.Conclusion:Few studies were found specifically studying maternal RA during pregnancy and NDDs in offspring. The studies pointed towards a moderately higher risk of these outcomes; however, reporting bias appears to be a problem. Additional studies of appropriate design and power are needed.
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Artritis Reumatoide/complicaciones , Trastornos del Neurodesarrollo/etiología , Efectos Tardíos de la Exposición Prenatal/etiología , Femenino , Humanos , Embarazo , Riesgo , Medición de RiesgoRESUMEN
INTRODUCTION: The unprecedented COVID-19 pandemic unveiled a strong need for advanced and informative surveillance tools. The Centre for Health Informatics (CHI) at the University of Calgary took action to develop a surveillance dashboard, which would facilitate the education of the public, and answer critical questions posed by local and national government. OBJECTIVES: The objective of this study was to create an interactive method of surveillance, or a "COVID-19 Tracker" for Canadian use. The Tracker offers user-friendly graphics characterizing various aspects of the current pandemic (e.g. case count, testing, hospitalizations, and policy interventions). METHODS: Six publicly available data sources were used, and were selected based on the frequency of updates, accuracy and types of data, and data presentation. The datasets have different levels of granularity for different provinces, which limits the information that we are able to show. Additionally, some datasets have missing entries, for which the "last observation carried forward" method was used. The website was created and hosted online, with a backend server, which is updated on a daily basis. The Tracker development followed an iterative process, as new figures were added to meet the changing needs of policy-makers. RESULTS: The resulting Tracker is a dashboard that visualizes real-time data, along with policy interventions from various countries, via user-friendly graphs with a hover option that reveals detailed information. The interactive features allow the user to customize the figures by jurisdiction, country/region, and the type of data shown. Data is displayed at the national and provincial level, as well as by health regions. CONCLUSION: The COVID-19 Tracker offers real-time, detailed, and interactive visualizations that have the potential to shape crucial decision-making and inform Albertans and Canadians of the current pandemic.
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AIMS: To investigate whether the benefits of switching to insulin degludec observed in the European retrospective chart review study EU-TREAT were dependent on the previous basal insulin used. METHODS: People with Type 1 or Type 2 diabetes were switched to insulin degludec from other basal insulins ≥6 months before data collection. Participants were stratified into three groups based on their previous basal insulin: insulin glargine 100 units/ml (Type 1: n=888; Type 2: n=259); insulin detemir (Type 1: n=726; Type 2: n=415); and neutral protamine Hagedorn (Type 1: n=53; Type 2: n=95). Their glycaemic control and hypoglycaemia incidence at 6 and 12 months post-switch vs pre-switch was then evaluated. RESULTS: Significant HbA1c reductions were achieved in all previous basal insulin groups for participants with Type 1 diabetes [insulin glargine 100 units/ml: -2.08 mmol/mol (-0.19%); insulin detemir: -2.40 mmol/mol (-0.22%)] and those with Type 2 diabetes [insulin glargine 100 units/ml: -5.90 mmol/mol (-0.54%); insulin detemir: -6.01 mmol/mol (-0.55%); neutral protamine Hagedorn: -2.73 mmol/mol (-0.25%)] at 6 months, except for the relatively small neutral protamine Hagedorn group in those with Type 1 diabetes [-1.75 mmol/mol (-0.16%)], where statistical significance was not reached. At 6 months in the Type 1 diabetes group, switching to insulin degludec from insulin glargine 100 units/ml resulted in significantly lower hypoglycaemia rates across all hypoglycaemia categories; for the insulin detemir group, this significance was also observed for severe and nocturnal non-severe hypoglycaemia, while the low number of people in the neutral protamine Hagedorn group resulted in nonsignificant reductions in hypoglycaemia rates. At 6 months in the people with Type 2 diabetes, switching to insulin degludec resulted in significantly lower rates of hypoglycaemia across all categories for all groups. Similar outcomes were observed at 12 months. CONCLUSIONS: Switching to insulin degludec from other basal insulins can improve glycaemic control and/or reduce hypoglycaemia risk in people with diabetes (although there was a nonsignificant reduction in HbA1c and hypoglycaemia rates for the neutral protamine Hagedorn group in Type 1 diabetes) under routine care.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina Glargina/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Adulto , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged PFS, HR=2.4 (1.2-4.9, P=0.014) and those with predicted sensitivity to bortezomib had a HR 5.7 (1.2-27, P=0.027). In case of predicted sensitivity to bortezomib, a better response to treatment was found (P=0.022). This method may provide us with a tool for identifying candidates for effective personalized medicine and spare potential non-responders from suffering toxicity.
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Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Supervivencia sin Enfermedad , Perfilación de la Expresión Génica/métodos , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Transcriptoma/efectos de los fármacos , Transcriptoma/genéticaRESUMEN
We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in subjects with type 2 diabetes (T2D) and examined the influence of subjects' diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with glucagon-like peptide-1 (GLP-1) infusion and arginine injection, the morning after a 1-h walk or no exercise. Subjects were stratified by high and low fasting plasma glucose (FPG) levels and by glycated haemoglobin (HbA1c) levels, as well as by current use/non-use of antidiabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (p < 0.05 to <0.01). In subjects with low FPG levels, exercise increased GLP-1-stimulated insulin secretion (p < 0.05), with the same trend being observed for arginine (p = 0.08). The same trends were seen for subjects with low HbA1c levels. Furthermore, exercise increased GLP-1- and arginine-stimulated insulin secretion (p < 0.05) in subjects who were antidiabetic drug-naïve. Exercise-induced increases in insulin secretion are blunted in subjects with T2D with high rates of hyperglycaemia and in those using antidiabetic drugs.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ejercicio Físico , Glucagón/metabolismo , Hiperglucemia/prevención & control , Insulina/metabolismo , Páncreas/metabolismo , Arginina/administración & dosificación , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/terapia , Ayuno , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Técnica de Clampeo de la Glucosa , Humanos , Infusiones Intravenosas , Inyecciones , Insulina/sangre , Secreción de Insulina , Masculino , Páncreas/fisiopatología , Resultado del TratamientoRESUMEN
AIM: To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor. METHODS: In a multicentre study 123 MFS patients (n = 52 with AR, n = 71 without AR), 82 age- and sex-matched controls and 51 patients with AR but without MFS, were interviewed using a semi-structured headache questionnaire. A multinomial logistic regression model was used to investigate risk factors for migraine with and without aura, adjusting for age and gender. RESULTS: Lifetime migraine prevalence was increased in female MFS patients (51%) compared to healthy female controls (29%), p = 0.017. In males lifetime migraine prevalence among MFS patients was only numerically increased. Lifetime prevalence of migraine with aura was increased among MFS patients compared to healthy controls both in males (19% vs. 3%, p = 0.048) and females (30% vs. 14%, p = 0.049). A history of AR, independently from MFS, gender and age, increased the lifetime prevalence of migraine with aura (OR 3.1 [1.2-8.0]). In all but one patient migraine started before the AR. CONCLUSIONS: The lifetime prevalence of migraine with aura, but not migraine without aura, is increased in patients with MFS. This association is driven by a history of AR. The replacement procedure itself is unlikely to be causally associated with migraine as in nearly all subjects, migraine started before the procedure. However this study adds to the evidence that underlying vessel wall pathology may be involved in migraine with aura.
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Aorta/cirugía , Síndrome de Marfan/complicaciones , Migraña con Aura/epidemiología , Adulto , Aorta/patología , Femenino , Humanos , Masculino , Síndrome de Marfan/patología , Síndrome de Marfan/cirugía , Prevalencia , Encuestas y CuestionariosRESUMEN
PURPOSE OF REVIEW: Sleep and the chronobiological disease cluster headache are believed to be interconnected. Despite efforts, the precise nature of the relationship remains obscured. A better understanding of this relation may lead to more effective therapeutic regimes for patients suffering from this debilitating disease. This review aims to evaluate the existing literature on the subject of cluster headache and sleep. LATEST FINDINGS: Several previous studies describe an association between episodic cluster headache and distinct macrostructural sleep phases. This association was not confirmed in a recent study of seven episodic cluster headache patients, but it was suggested that further studies into the correlation between cluster headache attacks and the microstructure of sleep are relevant. The connection between cluster headache and the hypocretins is currently under investigation. SUMMARY: There is evidence in favour of an association between episodic cluster headache and REM sleep whereas no such relation to chronic cluster headache has been reported. Particular features in the microstructure of sleep and arousal mechanisms could play a role in the pathogenesis of cluster headache. Reports indicate that cluster headache and obstructive sleep apnoea are associated. Single cases show improvement upon treatment of sleep apnoea, but the causal relationship remains in question.
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Cefalalgia Histamínica/fisiopatología , Fases del Sueño/fisiología , Cefalalgia Histamínica/etiología , Humanos , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/fisiopatologíaRESUMEN
Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease (CVD). We examined the predictive ability of 24-hour ambulatory pulse pressure (24-h PP), ambulatory arterial stiffness index (AASI) and diurnal blood pressure (BP) parameters for fatal and non-fatal CVD in patients with type 2 diabetes mellitus. A total of 108 patients with type 2 diabetes mellitus (mean duration 6.6 years) were followed for 9.5 (0.5-14.5) years. At baseline, all patients underwent ambulatory BP monitoring. During follow-up, 45 patients had cardiovascular (CV) events (35 non-fatal and 10 fatal). In bivariate analysis, events during follow-up were predicted by 24-h PP (P<0.01), AASI, 24-h systolic BP and systolic and diastolic night-day BP ratio (P<0.05 for all). In Cox regression analysis adjusted for established risk markers, only 24-h PP and systolic night-day BP ratio predicted CV events, P<0.05 for both. A significant interaction between the two parameters was found, P<0.05; thus, the higher the systolic night-day ratio, the greater the increase in hazard ratio (HR) per mmHg increase in 24-h PP and vice versa. A combined 10 mmHg increase in 24-h PP and 10%-point increase in systolic night-day ratio from the 25th percentile increased the adjusted HR (95% confidence interval) for CV events with 1.29 (0.53; 3.12), whereas a similar increase from the 75th percentile increased the HR with 4.2 (1.54; 11,51). Our study showed that 24-h PP and systolic night-day ratio interact as predictors of CV events in type 2 diabetes patients, and should be considered in conjunction when evaluating the risk of CVD.
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Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/epidemiología , Ritmo Circadiano/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/fisiopatología , Anciano , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
A herd of red deer experienced a small outbreak of atypical interstitial pneumonia on two occasions 3 years apart. The first occasion involved the death of two of a group of 70 hinds and the second outbreak involved a single death in a similar sized group. On both occasions a number of the adults exhibited increased respiratory effort, particularly on exercise. Both outbreaks occurred in July, a few days after moving the herd from a close grazed grass paddock to an aftermath paddock, which had regrown to a good sward. The history and pathology is reminiscent of 3-methyl indole toxicity in cattle.
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Ciervos , Brotes de Enfermedades , Enfermedades Pulmonares Intersticiales/veterinaria , Animales , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/patología , Escatol/toxicidad , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC. METHODS: 2 NC children received IVIG 1 g/kg/day in 2 days/month, 5 times, at 3 and 6 months disease duration, respectively. CSF and serum were analysed for hypocretin neuron autoantibodies. An association between disease duration and IVIG effect was calculated in all published NC cases. RESULTS: Autoantibodies were not detectable. Cataplexy improved in both children but only temporarily in one patient. Subjective sleepiness temporarily improved, sleep paralysis emerged and hypnagogic hallucinations and REM sleep behaviour disorder worsened in one child. Sleep parameters and CSF hypocretin-1 remained abnormal. On a group level, IVIG treatment ≤ 9 months from disease duration predicted reduction of cataplexy (p=0.004) and sleepiness (p=0.066). Sleep parameters and CSF hypocretin-1 levels were unchanged except if treated extremely early. CONCLUSION: IVIG treatment initiated before 9 months disease duration has some clinical efficiency. The unaffected CSF hypocretin-1 levels and lack of autoantibodies suggest that any autoimmune process occurs very early in NC. The final IVIG effect needs to be investigated in a placebo-controlled study.
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Autoanticuerpos/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/inmunología , Narcolepsia/terapia , Neuronas/inmunología , Neuropéptidos/inmunología , Adolescente , Niño , Femenino , Humanos , Masculino , Narcolepsia/diagnóstico , Narcolepsia/inmunología , Orexinas , Sueño/inmunología , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Inflammatory bowel disease (IBD) is a multifactorial disorder with an unknown aetiology. The aim of this study is to employ a murine model of IBD to identify pathways and genes, which may play a key role in the pathogenesis of IBD and could be important for discovery of new disease markers in human disease. Here, we have investigated severe combined immunodeficient (SCID) mice, which upon adoptive transfer with concanavalin A-activated CD4(+) T cells develop inflammation of the colon with predominance in rectum. Mice with increasing level of inflammation was studied. RNA from rectum of transplanted and non-transplanted SCID mice was investigated by a genome-wide gene expression analysis using the Affymetrix mouse expression array 430A (MOE430A) including 22,626 probe sets. A significant change in gene expression (P = 0.00001) is observed in 152 of the genes between the non-transplanted control mice and colitis mice, and among these genes there is an overrepresentation of genes involved in inflammatory processes. Some of the most significant genes showing higher expression encode S100A proteins and chemokines involved in trafficking of leucocytes in inflammatory areas. Classification by gene clustering based on the genes with the significantly altered gene expression corresponds to two different levels of inflammation as established by the histological scoring of the inflamed rectum. These data demonstrate that this SCID T-cell transfer model is a useful animal model for human IBD and can be used for suggesting candidate genes involved in the pathogenesis and for identifying new molecular markers of chronic inflammation in human IBD.
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Colitis/genética , Perfilación de la Expresión Génica/métodos , Genoma , Linfocitos T/inmunología , Traslado Adoptivo/efectos adversos , Animales , Mapeo Cromosómico , Análisis por Conglomerados , Colitis/etiología , Colitis/inmunología , Colon/metabolismo , Colon/patología , Concanavalina A/inmunología , Femenino , Genoma Humano , Humanos , Enfermedades Inflamatorias del Intestino/genética , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sintenía , Linfocitos T/trasplanteRESUMEN
AIMS/HYPOTHESIS: We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. METHODS: Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. RESULTS: At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001). CONCLUSIONS/INTERPRETATION: Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.
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Presión Sanguínea/fisiología , Ritmo Circadiano , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Pulso Arterial , Edad de Inicio , Anciano , Albuminuria , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Creatinina/orina , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/orina , Progresión de la Enfermedad , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/métodos , Análisis de RegresiónRESUMEN
There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system has been reported in MS case reports with attacks of hypothalamic lesions, undetectable cerebrospinal fluid (CSF) hcrt-1 and hypersomnia, but not found during remission in small samples. Finally, daytime sleepiness, the major symptom of narcolepsy, is reported in several MS populations, and there are case reports of co-existent narcolepsy and MS. However, it is unknown whether hcrt-1 and daytime sleepiness generally change during MS attacks. We therefore analyzed whether daytime sleepiness (using the Epworth Sleepiness Scale (ESS)) and CSF hcrt-1 levels differed between MS attack and remission, in 48 consecutively referred patients with relapsing-remitting MS (RRMS) or monosymptomatic optic neuritis (MON). Twenty-seven patients were in attack and 21 in remission. ESS was normal both during attacks (5.4 +/- 3.0) and remission (5.8 +/- 2.6), and mean CSF hcrt-1 was normal (456 +/- 41 pg/ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI.
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Trastornos de Somnolencia Excesiva/fisiopatología , Péptidos y Proteínas de Señalización Intracelular/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Neuropéptidos/líquido cefalorraquídeo , Neuritis Óptica/fisiopatología , Fases del Sueño/fisiología , Adulto , Trastornos de Somnolencia Excesiva/líquido cefalorraquídeo , Trastornos de Somnolencia Excesiva/etiología , Femenino , Humanos , Hipotálamo/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/etiología , Orexinas , RecurrenciaRESUMEN
AIM: Elevated pulse pressure (PP) is associated with microvascular complications in Type 2 diabetic patients. In non-diabetic subjects, elevated PP has been associated with endothelial dysfunction. The relation between endothelial dysfunction and PP in diabetic subjects has not previously been examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group A; e.g. ICAM-1 [median (interquartile range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r = 0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1, respectively). CONCLUSION: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate these associations.
Asunto(s)
Albuminuria/fisiopatología , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Anciano , Monitoreo Ambulatorio de la Presión Arterial/métodos , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor de von Willebrand/análisisRESUMEN
Liparidae (snailfishes) is one of the most diverse and abundant fish families in polar and deep-sea habitats. However, the evolution of this family is poorly known because of the rarity of many species and difficulties in scoring morphological characters. We perform phylogenetic analyses of Liparidae using sequences from two mtDNA genes, 16S (585 bp) and cytochrome b (426 bp), and 84 morphological characters from 24 species of Liparidae and 4 species of Cyclopteridae (outgroup). The present study confirms earlier hypotheses that the shallow-water genera, such as Liparis and Crystallichthys, occupy basal positions and that deep-water genera, such as Careproctus, Elassodiscus, Rhinoliparis, Paraliparis, Rhodichthys and Psednos, are increasingly derived. The later two genera form a terminal clade which does not include Paraliparis. The topology shows that the family has undergone a reductive type of evolution, with a gradual loss of characters (e.g. sucking disc/pelvic fins, pseudobranchial filaments, skin spinules). Nectoliparis, which had previously been placed either as the basal most genus or among the most derived genera, are found to occupy the most basal position among the taxa analyzed. This result indicates that the sucking disc has been lost at least twice during the evolution of the Liparidae. The basal position of Nectoliparis is supported by its plesiomorphic otolith morphology, whereas an advanced overgrown otolith ostium, unique among teleosts, is found to be apomorphic for a clade containing the derived genera: Paraliparis, Psednos, Rhinoliparis and Rhodichthys. We also identify the presence of probable nuclear inserts of mitochondrial DNA (Numts) in three species of Careproctus and in Elassodiscus caudatus.
Asunto(s)
Filogenia , Vertebrados/crecimiento & desarrollo , Vertebrados/genética , Animales , Secuencia de Bases , Citocromos b/genética , ARN Ribosómico 16S/genéticaRESUMEN
OBJECTIVE: Plasma levels of osteoprotegerin (OPG) are elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. In previous studies a positive correlation was found between plasma levels of OPG and markers of glycaemic control in diabetic subjects. The aim of the present study was to examine the effect of acute hyperglycaemia on plasma levels of OPG in non-diabetic subjects. MATERIAL AND METHODS: Nine healthy, lean, male subjects were examined in a randomized, blinded, cross-over study design during hyperglycaemic (plasma glucose = 15 mmol/L, study H) as well as during euglycaemic (plasma glucose = 5 mmol/L, study E) conditions. Blood samples were collected at baseline and at t=240 min. RESULTS: Plasma OPG decreased slightly during study H (1.26+/-0.39 versus 1.19+/-0.35 ng/mL, p<0.05), whereas the level did not change significantly during study E (1.40+/-0.46 ng/mL versus 1.57+/-0.50 ng/mL, NS). The decrease in plasma OPG during hyperglycaemia did not correlate with the change in plasma glucose but correlated significantly with changes in serum insulin (r=-0.70, p=0.038). CONCLUSIONS: Acute hyperglycaemia does not seem to increase plasma levels of OPG in non-diabetic subjects, whereas hyperinsulinaemia may suppress plasma levels of OPG. This finding indicates that the elevated plasma levels of OPG observed in diabetic subjects with poor metabolic control cannot be ascribed to hyperglycaemia per se.