RESUMEN
BACKGROUND: Intralymphatic immunotherapy (ILIT) is a novel, faster alternative to conventional allergen immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the present study was to complete a 5-year follow-up of a randomized double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. METHODS: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U administered in 3 intralymphatic injections at 1-month intervals. A year after the vaccination, the symptoms induced by nasal provocation were significantly reduced. After 5-6 years, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT) and seasonal registration of the combined symptom and medications score (CSMS), IgE and IgG4 levels in blood, and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls. RESULTS: The reduction in the NPT response with ILIT at year 1 could not be convincingly reproduced at year 5. The new CSMS scores were markedly lower among the previously treated patients than among the control group. Furthermore, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils was reduced, and the fraction of memory T-cells in lymph nodes increased. CONCLUSION: The combination of seasonal clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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Rinitis Alérgica Estacional , Rinitis Alérgica , Humanos , Poaceae , Betula , Estudios de Seguimiento , Alérgenos , Desensibilización Inmunológica/efectos adversos , Rinitis Alérgica/tratamiento farmacológico , Inmunoglobulina E , Inmunoglobulina G , Método Doble CiegoRESUMEN
Background: The current standard for evaluating axillary nodal burden in clinically node negative breast cancer is sentinel lymph node biopsy (SLNB). However, the accuracy of SLNB to detect nodal stage N2-3 remains debatable. Nomograms can help the decision-making process between axillary treatment options. The aim of this study was to create a new model to predict the nodal stage N2-3 after a positive SLNB using machine learning methods that are rarely seen in nomogram development.Material and methods: Primary breast cancer patients who underwent SLNB and axillary lymph node dissection (ALND) between 2012 and 2017 formed cohorts for nomogram development (training cohort, N = 460) and for nomogram validation (validation cohort, N = 70). A machine learning method known as the gradient boosted trees model (XGBoost) was used to determine the variables associated with nodal stage N2-3 and to create a predictive model. Multivariate logistic regression analysis was used for comparison.Results: The best combination of variables associated with nodal stage N2-3 in XGBoost modeling included tumor size, histological type, multifocality, lymphovascular invasion, percentage of ER positive cells, number of positive sentinel lymph nodes (SLN) and number of positive SLNs multiplied by tumor size. Indicating discrimination, AUC values for the training cohort and the validation cohort were 0.80 (95%CI 0.71-0.89) and 0.80 (95%CI 0.65-0.92) in the XGBoost model and 0.85 (95%CI 0.77-0.93) and 0.75 (95%CI 0.58-0.89) in the logistic regression model, respectively.Conclusions: This machine learning model was able to maintain its discrimination in the validation cohort better than the logistic regression model. This indicates advantages in employing modern artificial intelligence techniques into nomogram development. The nomogram could be used to help identify nodal stage N2-3 in early breast cancer and to select appropriate treatments for patients.
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Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Ganglios Linfáticos/patología , Aprendizaje Automático , Nomogramas , Adulto , Anciano , Anciano de 80 o más Años , Axila , Biopsia con Aguja Fina , Mama/patología , Carcinoma Ductal de Mama/secundario , Femenino , Humanos , Modelos Logísticos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Persona de Mediana Edad , Invasividad Neoplásica , Curva ROC , Análisis de Regresión , Estudios Retrospectivos , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela , Carga TumoralRESUMEN
Objective: To describe health care resource utilization (HCRU) and associated costs in adult patients referred for specialist asthma care in Southwest Finland, by disease severity and blood eosinophil count (BEC).Methods: This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from patients >18 years of age on the hospital register of the Hospital District of Southwest Finland. Data extraction was from January 1, 2004 to December 31, 2015; the index date was the first hospital visit within this period with an International Classification of Diseases-10 diagnosis code for asthma or acute severe asthma. Patients were categorized by asthma severity (based on medication use) and BEC (<300 or ≥300 cells/µL). Total and asthma-related HCRU and estimated costs were recorded the year following index and for calendar years 2004-2015.Results: Overall, 14,398 patients were included; 388 had severe asthma at index. BEC was available for 3781 patients; 1434 had a BEC ≥300 cells/µL and 2347 had a BEC <300 cells/µL. A total of 1241 patients had severe asthma; 270 patients had severe eosinophilic asthma (severe asthma and a BEC ≥300 cells/µL). Patients with severe versus non-severe asthma had higher total- and asthma-related outpatient visits, inpatient days, emergency room visits and costs per patient year; those with BEC ≥300 cells/µL versus <300 cells/µL had more outpatient visits. All recorded HCRU and associated costs were highest in patients with severe eosinophilic asthma.Conclusion: This study demonstrated a substantial burden associated with severe and/or eosinophilic asthma for adults in Finland.
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Asma/economía , Asma/epidemiología , Eosinofilia/epidemiología , Gastos en Salud/estadística & datos numéricos , Recursos en Salud/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/fisiopatología , Índice de Masa Corporal , Costo de Enfermedad , Costos y Análisis de Costo , Eosinófilos/metabolismo , Femenino , Finlandia , Recursos en Salud/economía , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Transcriptional factor p53 is a master regulator of energy metabolism. Energy metabolism strongly depends on thiamine (vitamin B1) and/or its natural derivatives. Thiamine diphosphate (ThDP), which is a major thiamine derivative, affects p53 binding to DNA. In order to elucidate the mechanism of regulation of thiamine-dependent metabolism by p53, we assessed putative p53-binding sites near transcription starting points in genes coding for transporters and enzymes, whose function is associated with thiamine and/or its derivatives. The predictions were validated by studying cell metabolic response to the p53 inducer cisplatin. Expression of p53 and its known target, p21, has been evaluated in cisplatin-treated and control human lung adenocarcinoma A549 cells that possess functional p53 pathway. We also investigated the activity of enzymes involved in the thiamine-dependent energy metabolism. Along with upregulating the expression of p53 and p21, cisplatin affected the activities of metabolic enzymes, whose genes were predicted as carrying the p53-binding sites. The activity of glutamate dehydrogenase GDH2 isoenzyme strongly decreased, while the activities of NADP+-dependent isocitrate dehydrogenase (IDH) and malic enzymes, as well as the activity of 2-oxoglutarate dehydrogenase complex at its endogenous ThDP level, were elevated. Simultaneously, the activities of NAD+-dependent IDH, mitochondrial aspartate aminotransferase, and two malate dehydrogenase isoenzymes, whose genes were not predicted to have the p53-binding sequences near the transcription starting points, were upregulated by cisplatin. The p53-dependent regulation of the assayed metabolic enzymes correlated with induction of p21 by p53 rather than induction of p53 itself.
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Tiamina/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Células A549 , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/metabolismo , Cisplatino/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Metabolismo Energético , Glutamato Deshidrogenasa/metabolismo , Humanos , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Oxidación-Reducción , Tiamina Pirofosfato/metabolismoRESUMEN
High pressure (HP) treatment often results in discoloration of beef, lamb, pork, and poultry. The degree of color changes depends on the physical and chemical state of the meat, especially myoglobin, and the atmospheric conditions during and after pressurization. A decreased redness is attributed to a large degree to the oxidation of the bright red oxymyoglobin or the purplish deoxymyoglobin into the brownish metmyoglobin, as well as to the denaturation of myoglobin. Surely, the high myoglobin content makes beef more exposed to this discoloration compared to the white chicken meat. In addition, HP treatment causes denaturation of myofibrillar proteins followed by aggregation, consequently, changing the surface reflectance and increasing lightness. Other intrinsic and extrinsic factors may affect the pressure-induced color changes positively or negatively. In this review, the pressure-induced color changes in meat are discussed in relation to modification of the myoglobin molecule, changes in the meat microstructure, and the impact of the presence of different chemical compounds and physical conditions during processing.
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Color , Manipulación de Alimentos/métodos , Productos de la Carne/análisis , Carne/análisis , Presión , Animales , Bovinos , Pollos , Metamioglobina/análisis , Músculo Esquelético/química , Mioglobina/análisis , Mioglobina/química , Oxidación-Reducción , Carne Roja/análisis , Ovinos , PorcinosRESUMEN
BACKGROUND: The prevalence of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is unknown. Although an uncommon condition, it is considered to be the most common autoinflammatory disease among children in many parts of the world. The knowledge of the consequences of the recurrent fever episodes for the child and its family are limited. This study explores the experiences of parents regarding the impact of the disease on the child's general well-being, the family's situation and how the family handles the associated challenges. METHODS: A qualitative approach was used, applying a modified version of Grounded theory for design, data collection and analysis. Data was collected from two different sources: communication between parents of children with PFAPA in a closed Facebook group and face-to face interviews with one of the parents of children diagnosed with PFAPA (6 mothers and 2 fathers). RESULTS: Parents described a lengthy process of how everyday life becomes affected by their child's recurrent fever episodes. This process is depicted in the following Grounded Theory core category: From uncertainty to gradually managing and awaiting recovery. The categories Uncertainty, Assurance, Gradually managing and Recovery describe the experienced illness trajectory. The illness representation illustrates the experiences/impacts of the periodic condition in the subcategories: Harmlessness-Severity, Disclosure of diagnosis, Impact on daily life and Regularity-Unpredictability. The children's well-being was highly affected by the symptoms during episodes. Parents experienced increased stress with constant fatigue, social constraints of family life and restricted career opportunities. Nevertheless, hope of recovery was constantly present. CONCLUSIONS: PFAPA is associated with a considerable burden on the child and the parents in daily life. Obtaining a diagnosis enables parents to move from a state of uncertainty towards a sense of coherence while awaiting recovery. Because of limited general knowledge of the condition and its impact on daily life, health care professionals need to become aware of the parents' efforts to mitigate the consequences of the recurrent episodes for the child and for the family as a whole.
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Fiebre , Linfadenitis , Padres , Faringitis , Calidad de Vida , Estomatitis Aftosa , Adulto , Niño , Preescolar , Femenino , Humanos , Entrevistas como Asunto , Masculino , Padres/psicología , Periodicidad , Medios de Comunicación Sociales , Síndrome , IncertidumbreRESUMEN
OBJECTIVES: Acute lower limb ischaemia (ALLI) is a potentially fatal, limb threatening medical emergency. Early treatment is essential for a good outcome. The aim was to describe the early chain of care in ALLI focusing on lead times and emergency management in order to identify weak links for improvement. METHODS: This was a retrospective, descriptive case study. This study analysed the medical records of all patients with a main discharge diagnosis of ALLI between January 2009 and December 2014. Predetermined emergency care data on lead times, diagnosis recognition, presenting symptoms, emergency care treatment and outcome were collected for patients who were transported by the Emergency Medical Service (EMS) and those who were not. RESULTS: In total, 552 medical records were audited of which 195 patients fulfilled the inclusion criteria and were analysed. Among them were 117 (60%) transported by the EMS. The median time from symptom onset to revascularisation was 23 (interquartile range [IQR] 10-55; EMS transported) and 93 (IQR 42-152, not EMS transported) hours (p < .01). The time from symptom onset to arrival in hospital was 5 (IQR 2-26; EMS transported) and 48 (IQR 6-108; not EMS transported) hours. After arrival in hospital, the median time to first doctor evaluation was 51 (IQR 28-90; EMS transported) and 80 (IQR 44-169; not EMS transported) minutes, p = .01. Low molecular weight heparin (LMWH) was given to 72% of patients in the emergency department (ED) and a multivariate analysis showed that the use of LMWH was associated with a more favourable outcome. CONCLUSIONS: Both the time spent in the ED and the time from the onset of symptoms to revascularisation were considerably longer than optimal. Time delays in the early treatment chain can mainly be attributed to "patient delay" and a considerable time spent in hospital before revascularisation. The use of LMWH as an integral part of ED management was associated with a better outcome.
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Anticoagulantes/administración & dosificación , Vías Clínicas , Servicios Médicos de Urgencia , Heparina de Bajo-Peso-Molecular/administración & dosificación , Isquemia/diagnóstico , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Diagnóstico Precoz , Femenino , Humanos , Isquemia/fisiopatología , Recuperación del Miembro , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tiempo de Tratamiento , Resultado del Tratamiento , Triaje , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
BACKGROUND: Dissecting the role copy number variants (CNVs) play in disease pathogenesis is directly reliant on accurate methods for quantification. The Shar-Pei dog breed is predisposed to a complex autoinflammatory disease with numerous clinical manifestations. One such sign, recurrent fever, was previously shown to be significantly associated with a novel, but unstable CNV (CNV_16.1). Droplet digital PCR (ddPCR) offers a new mechanism for CNV detection via absolute quantification with the promise of added precision and reliability. The aim of this study was to evaluate ddPCR in relation to quantitative PCR (qPCR) and to assess the suitability of the favoured method as a genetic test for Shar-Pei Autoinflammatory Disease (SPAID). RESULTS: One hundred and ninety-six individuals were assayed using both PCR methods at two CNV positions (CNV_14.3 and CNV_16.1). The digital method revealed a striking result. The CNVs did not follow a continuum of alleles as previously reported, rather the alleles were stable and pedigree analysis showed they adhered to Mendelian segregation. Subsequent analysis of ddPCR case/control data confirmed that both CNVs remained significantly associated with the subphenotype of fever, but also to the encompassing SPAID complex (p < 0.001). In addition, harbouring CNV_16.1 allele five (CNV_16.1|5) resulted in a four-fold increase in the odds for SPAID (p < 0.001). The inclusion of a genetic marker for CNV_16.1 in a genome-wide association test revealed that this variant explained 9.7 % of genetic variance and 25.8 % of the additive genetic heritability of this autoinflammatory disease. CONCLUSIONS: This data shows the utility of the ddPCR method to resolve cryptic copy number inheritance patterns and so open avenues of genetic testing. In its current form, the ddPCR test presented here could be used in canine breeding to reduce the number of homozygote CNV_16.1|5 individuals and thereby to reduce the prevalence of disease in this breed.
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Enfermedades Autoinmunes/veterinaria , Variaciones en el Número de Copia de ADN , Enfermedades de los Perros/genética , Reacción en Cadena de la Polimerasa/métodos , Alelos , Animales , Enfermedades Autoinmunes/genética , Perros , Variación Genética , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Homocigoto , Linaje , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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Enfermedad de Addison/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Exoma/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Haplotipos , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Análisis de Secuencia , Adulto JovenRESUMEN
Two experiments were carried out in parallel with male Ross 308 broilers over 37 d. An experiment with a total of 736 broilers was performed to study the effect of dietary inclusion of crimped kernel maize silage (CKMS) on broiler production and meat quality. Another study with 32 broilers was carried out from 21 to 25 d to investigate the inclusion of CKMS on nutrient digestibility. In both trials, 4 dietary treatments were used: wheat-based feed (WBF), maize-based feed (MBF), maize-based feed supplemented with 15% CKMS (CKMS-15) and maize-based feed supplemented with 30% CKMS (CKMS-30). Compared with MBF, the dry matter (DM) intakes of broilers receiving CKMS-15 and CKMS-30, respectively, were numerically 7.5 and 6.2% higher and feed conversion ratio 6 and 12% poorer (significant for 30% CKMS), although there were no significant differences in AME content between the three diets. At 37 d, the body weight of birds receiving 15% CKMS was similar to birds fed with MBF. However, the inclusion of 30% CKMS decreased broiler growth. Dietary supplementation with CKMS significantly reduced the apparent digestibility of phosphorus. The fat digestibility was significantly lower for CKMS-30 than for the other three diets. Broiler mortality decreased significantly when CKMS was added to the diet. The consumption of drinking water was significantly lower in all maize-based diets as compared to WBF and was lowest in broilers fed with CKMS-30. An improved litter quality in terms of DM content and a lower frequency of foot pad lesions was observed with broilers supplemented with both dietary levels of CKMS. The addition of CKMS to maize-based diets increased juiciness, tenderness and crumbliness of the meat. In conclusion, the dietary supplementation of 15% CKMS had no negative effect on broiler growth and positively influenced bird welfare in terms of mortality and foot pad health. Therefore, the addition of 15% CKMS to maize-based diets is considered an advantageous feeding strategy in broiler production.
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Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Pollos/fisiología , Digestión/efectos de los fármacos , Carne/análisis , Ensilaje/análisis , Zea mays/química , Animales , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Masculino , Distribución AleatoriaRESUMEN
BACKGROUND: We have shown previously that honokiol (HNK), a bioactive component of the medicinal plant Magnolia officinalis, inhibits growth of human prostate cancer cells in vitro and in vivo. However, the effect of HNK on androgen receptor (AR) signaling has not been studied. METHODS: LNCaP, C4-2, and TRAMP-C1 cells were used for various assays. Trypan blue dye exclusion assay or clonogenic assay was performed for determination of cell viability. The effects of HNK and/or its analogs on protein levels of AR and its target gene product prostate specific antigen (PSA) were determined by western blotting. RNA interference of p53 was achieved by transient transfection. Reverse transcription-polymerase chain reaction was performed for mRNA expression of AR. Nuclear level of AR was visualized by microscopy. Apoptosis was quantified by DNA fragmentation assay or flow cytometry after Annexin V-propidium iodide staining. RESULTS: HNK and its dichloroacetate analog (HDCA) were relatively more effective in suppressing cell viability and AR protein level than honokiol epoxide or biseugenol. Nuclear translocation of AR stimulated by a synthetic androgen (R1881) was markedly suppressed in the presence of HNK. Downregulation of AR protein resulting from HNK exposure was attributable to transcriptional repression as well as proteasomal degradation. HNK-mediated suppression of AR protein was maintained in LNCaP cells after knockdown of p53 protein. HNK-induced apoptosis was not affected by R1881 treatment. CONCLUSIONS: The present study demonstrates, for the first time, that HNK inhibits activity of AR in prostate cancer cells regardless of the p53 status.
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Compuestos de Bifenilo/farmacología , Regulación hacia Abajo/efectos de los fármacos , Lignanos/farmacología , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , MasculinoRESUMEN
STUDY DESIGN: Clinical experimental mechanistic study. OBJECTIVES: (1) To determine in three spinal cord-injured patients whether individual muscle sympathetic nerve fibres below the level of the spinal lesion display spontaneous activity. (2) To determine in these patients if individual sympathetic vasoconstrictor fibres show a prolonged discharge following a bladder stimulus. SETTING: University hospital in Gothenburg, Sweden. METHODS: Microneurographic recordings of action potentials from individual muscle nerve sympathetic fibres in a peroneal nerve. Recordings of skin blood flow and electrodermal responses in a foot. RESULTS: In all patients, there was sparse ongoing spontaneous impulse traffic in individual sympathetic fibres. Brisk mechanical pressure over the urinary bladder evoked a varying number of action potentials in individual fibres, but the activity was brief and did not continue after the end of the evoked multiunit burst. CONCLUSION: Prolonged discharges in individual sympathetic fibres are unlikely to contribute to a long duration of blood pressure increases induced by brief bladder stimuli.
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Axones/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Tacto/fisiología , Vejiga Urinaria/fisiopatología , Potenciales de Acción , Adulto , Femenino , Respuesta Galvánica de la Piel/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estimulación Física , Flujo Sanguíneo Regional/fisiología , Descanso , Piel/irrigación sanguínea , Piel/fisiopatologíaRESUMEN
Polyhydroxyalkanoates (PHAs) are biodegradable polyesters with comparable properties to some petroleum-based polyolefins. PHA production can be achieved in open, mixed microbial cultures and thereby coupled to wastewater and solid residual treatment. In this context, waste organic matter is utilised as a carbon source in activated sludge biological treatment for biopolymer synthesis. Within the EU project Routes, the feasibility of PHA production has been evaluated in processes for sludge treatment and volatile fatty acid (VFA) production and municipal wastewater treatment. This PHA production process is being investigated in four units: (i) wastewater treatment with enrichment and production of a functional biomass sustaining PHA storage capacity, (ii) acidogenic fermentation of sludge for VFA production, (iii) PHA accumulation from VFA-rich streams, and (iv) PHA recovery and characterisation. Laboratory- and pilot-scale studies demonstrated the feasibility of municipal wastewater and solid waste treatment alongside production of PHA-rich biomass. The PHA storage capacity of biomass selected under feast-famine with municipal wastewater has been increased up to 34% (g PHA g VSS(-1)) in batch accumulations with acetate during 20 h. VFAs obtained from waste activated sludge fermentation were found to be a suitable feedstock for PHA production.
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Polihidroxialcanoatos/metabolismo , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodosRESUMEN
Introduction: Use of amphetamine-type stimulants (ATS) contributes substantially to the global burden of disease. Large-scale follow-up studies of morbidity and mortality in ATS users are few. This study analysed morbidity, mortality, and potential predictors of all-cause mortality in a nationwide cohort of patients with ATS use disorder. Methods: Data was acquired from national Swedish registers. All Swedish residents 18 years or older, with a registered ATS use diagnosis in 2013-2014 were included (N = 5,018) and followed until December 31, 2017. Comorbid diagnoses and causes of death were assessed and potential predictors of all-cause mortality were examined through Cox regression. Results: Median age at inclusion was 36.6 years (interquartile range 27.4---48.1) and 70.5 % were men. The crude mortality rate was 24.6 per 1,000 person-years. The adjusted all-cause standardized mortality ratio was 12.4 (95 % CI [11.34-13.55]). The most common cause of death was overdose (28.9 %). Multiple drug use (hazard ratio 1.39, 95 % CI [1.14-1.70], p = 0.004), anxiety (hazard ratio 1.39, 95 % CI [1.11-1.72], p = 0.014), viral hepatitis (hazard ratio 1.85, 95 % CI [1.50-2.29], p = 0.004), and liver disease (hazard ratio 2.41, 95 % CI [1.55-3.74], p = 0.004) were predictors of all-cause mortality. Conclusions: Multiple drug use, anxiety disorders, viral hepatitis and liver diseases were identified as risk factors for death. Our findings call for better screening, prevention, and treatment of somatic and psychiatric comorbidity among ATS users to reduce mortality.
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OBJECTIVE: Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes human leukocyte antigen DQ (HLA-DQ) risk genotypes may be associated with increased body mass index (BMI). DESIGN: The type 1 diabetes high-risk HLA-DQ A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by PCR and hybridization with allele-specific probes. BMI was determined after diabetes was stabilized. SUBJECTS: A total of 2403 incident type 1 diabetes children below 18 years of age were ascertained in the Swedish national Better Diabetes Diagnosis (BDD) study between May 2005 to September 2009. All children classified with type 1 diabetes, including positivity for at least one islet autoantibody, were investigated. RESULTS: Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI (P<0.0008). The proportion of the highest risk A1*05:01-B1*02:01/A1*03:01-B1)03:02 genotype decreased with increasing BMI (P<0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (P<0.0001). Indeed, the proportion of patients with the low-risk A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype increased with increasing BMI (P<0.003). The magnitude of association on the multiplicative scale between the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and increased BMI was significant (P<0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21-2.61; P<0.006). The increased proportion of overweight type 1 diabetes children with the A1*05:01-B1*02:01 haplotype was most pronounced in children diagnosed between 5 and 9 years of age. CONCLUSIONS: Susceptibility for childhood type 1 diabetes was unexpectedly found to be associated with the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and an increased BMI. These results support the hypothesis that overweight may contribute to the risk of type 1 diabetes in children positive for HLA-DQ A1*05:01-B1*02:01.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-DQ/genética , Haplotipos , Obesidad/genética , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Obesidad/epidemiología , Oportunidad Relativa , Estudios Prospectivos , Suecia/epidemiologíaRESUMEN
AIM: To investigate the development of waist circumference (WC) in preschool children born preterm compared with a population-based reference. BACKGROUND: Children born preterm are reported to be insulin resistant, despite being lean during early childhood. We hypothesize that the mechanism is through increased visceral adiposity. METHODS: Data from 4446 preschool children (2169 girls/2277 boys) born in 2001-2006 from a population-based study were compared with longitudinal measurements of body mass index (BMI) and WC from a cohort of 152 children (64 girls/88 boys) born moderately preterm in 2002-2004 (gestational age, 32-37 weeks). RESULTS: In the preterm children, the mean WC was 2.8 cm larger compared with the reference group (p < 0.001) at 2 years of age but not at 5 years of age. There was no significant difference in the mean BMI at 2 years of age. The preterm group was significantly leaner at 5 years of age, with a mean BMI of 15.13 compared with 15.98 in the reference group (p < 0.001). CONCLUSION: Children born moderately preterm present as lean during early childhood but have an increased waist circumference in infancy, pointing towards a change in fat distribution with more abdominal fat. This may have implications for their metabolic status.
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Índice de Masa Corporal , Desarrollo Infantil/fisiología , Recien Nacido Prematuro/crecimiento & desarrollo , Circunferencia de la Cintura , Estudios de Casos y Controles , Preescolar , Femenino , Gráficos de Crecimiento , Humanos , Lactante , Recién Nacido , Modelos Lineales , Estudios Longitudinales , MasculinoRESUMEN
OBJECTIVES: To create an international spinal cord injury (SCI) skin and thermoregulation basic data set within the framework of the International SCI Data Sets. SETTING: An international working group. METHODS: The draft of the data set was developed by a working group comprising members appointed by the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the Executive Committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review and comments by members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA Board, relevant and interested international organizations and societies, individual persons with specific interest and the ISCoS Council. To make the data set uniform, each variable and each response category within each variable have been specifically defined to promote the collection and reporting of comparable minimal data. RESULTS: Variables included in the present data set are: date of data collection, thermoregulation history after SCI, including hyperthermia or hypothermia (noninfectious or infectious), as well as the history of hyperhidrosis or hypohidrosis above or below level of lesion. Body temperature and the time of measurement are included. Details regarding the presence of any pressure ulcer and stage, location and size of the ulcer(s), date of appearance of the ulcer(s) and whether surgical treatment has been performed are included. The history of any pressure ulcer during the last 12 months is also noted.
Asunto(s)
Regulación de la Temperatura Corporal , Bases de Datos Factuales , Fiebre/fisiopatología , Hipotermia/fisiopatología , Temperatura Cutánea , Piel/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Fiebre/etiología , Humanos , Hipotermia/etiología , Internacionalidad , Traumatismos de la Médula Espinal/complicacionesRESUMEN
OBJECTIVES: To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. SETTING: International. METHODS: The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. RESULTS: The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion,if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk).
Asunto(s)
Bases de Datos Factuales , Enfermedades Respiratorias/etiología , Traumatismos de la Médula Espinal/complicaciones , HumanosRESUMEN
BACKGROUND: The way health care professionals touch patients and relatives in the intensive care unit plays a significant role. A negative feeling can be caused by being touched in the wrong way, this is why a holistic approach with respect for the patient is important for the ability to make the patient and their relatives feel secure, avoiding unnecessary suffering. AIM: The aim of the study was to describe the meaning of caring touch that is given in the ICU from the health care professionals perspective. METHOD: Qualitative interview study with health care professionals in the intensive care unit, analysed using inductive content analysis, resulting in two themes and four main categories. FINDINGS: Two themes emerged: Imperative touch and emotional touch and four main categories: touch as a natural tool, create a prerequisite for touch, empathetic touch and conversant touch. CONCLUSION: Caring touch can be used as a natural tool in the daily work in order to bring comfort and calm to the patient in the intensive care unit.
Asunto(s)
Unidades de Cuidados Intensivos , Tacto , Actitud del Personal de Salud , Personal de Salud , Humanos , Investigación CualitativaRESUMEN
In arctic charr Salvelinus alpinus, arterial blood partial pressures of oxygen (PaO2) and carbon dioxide increased with increasing water oxygen tension (PwO2), while the water to arterial PO2 difference (PwO2-PaO2) did not change in relation to PwO2.