Projected land ice contributions to twenty-first-century sea level rise.

The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2-8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.

The Association of Therapy Adherence and Thyroid Function in Adult Patients with Phenylketonuria.

BACKGROUND: The standard, lifelong therapy of phenylketonuria (PKU) is a natural protein-restricted diet complemented with phenylalanine (Phe)-free L-amino acid mixtures that provide the daily necessary micronutrients. OBJECTIVE: To assess thyroid function and structure and the iodine status of early-treated adult PKU (ETPKU) patients in Hungary. METHODS: Sixty-nine PKU patients (aged 18-41 years) and 50 healthy controls were enrolled in the study. Thyroid hormones, serum thyroglobulin, thyroid antibodies, urinary iodine, and selenium concentrations were measured, and thyroid ultrasound was performed. RESULTS: The incidence of thyroid dysfunction was infrequent (n = 2). Blood Phe was negatively correlated with thyroid-stimulating hormone (TSH), and PKU patients had higher free thyroxine and lower TSH levels than healthy controls. Although optimal iodine status was found in the entire PKU population, by dividing the patients according to their therapy compliance, we observed that lower therapy adherence was associated with mild iodine deficiency and lower urinary selenium levels. CONCLUSIONS: The results of this study suggest that iodine status is strongly influenced by the adherence to therapy in ETPKU patients. No or not enough medical food consumption combined with a low-Phe diet can lead to subclinical iodine deficiency.

[Maternal phenylketonuria]. / Maternális phenylketonuria.

Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This foetal damage is known as maternal phenylketonuria. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninaemia, should receive detailed counselling regarding their risks for adverse foetal effects, optimally before contemplating pregnancy. The most assured way to prevent maternal phenylketonuria is to maintain the maternal phenylalanine levels within the optimal range already before conception and throughout the whole pregnancy. Authors review the comprehensive programme for prevention of maternal phenylketonuria at the Metabolic Center of Budapest, they survey the practical approach of the continuous maternal metabolic control and delineate the outcome of pregnancies of mothers with phenylketonuria from the introduction of newborn screening until most recently.

Health Related Quality of Life assessment among early-treated Hungarian adult PKU patients using the PKU-QOL adult questionnaire.

BACKGROUND: The implementation of neonatal screening and the early initiation of lifelong therapy have helped to prevent severe complications and enabled much more favorable outcomes for early-treated phenylketonuria (ETPKU) patients. However, PKU patients tend to develop subtle cognitive and psychosocial abnormalities and the strict dietary therapy can present financial and social burden. Thus, PKU is expected to affect the quality of life (QoL) of these patients. There is insufficient evidence regarding the relationship between metabolic control and Health-Related QoL (HRQoL). We aimed to assess the effect of short- and long-term therapy on QoL among Hungarian adult PKU patients using the standardized PKU-specific PKU-QoL questionnaire. Methods: We conducted a single-centre, cross-sectional, observational study in Hungary. We included adult PKU patients treated with diet and amino acid supplements only. Patients reported HRQoL using the standardized adult PKU-QoL questionnaire and mean blood Phe concentrations were assessed for three different time periods: the previous 10 years, the previous year and concentration at the time of completing the questionnaire. The correlation between patients' QoL scores and their Phe levels was assessed. The classical PKU group was further divided into "good" and "suboptimal" adherence groups based on individual mean Phe levels in the examined time period. We evaluated differences in QoL among the two subgroups of classical PKU patients. QoL scores between classical and non-classical patients were also compared. Results: Data from 88 adult patients were analysed (66 had classical PKU). No median PKU-QoL score reached major or severe impact/frequent symptoms in any domain. The highest scores (meaning larger burden) were mostly related to emotional impact of PKU and disease management. When performing correlation analysis between Phe levels and QoL scores by all patients we found weak to fair positive correlation in several domains either short or long term. Patients with classical PKU reported greater financial impact of PKU than patients with less severe PKU. Classical PKU patients with good therapy adherence tended to report better HRQoL scores than patients with suboptimal adherence. Conclusion: We conclude that patients showed good HRQoL using the PKU-specific questionnaire. Our study demonstrates that suboptimal metabolic control is negatively associated with patients' HRQoL.

Metabolic and catecholamine response to sympathetic stimulation in early-treated adult male patients with phenylketonuria.

PURPOSE: Defective function of phenylalanine hydroxylase in phenylketonuria (PKU) results in the accumulation of phenylalanine (Phe) and the reduction of tyrosine (Tyr) in the blood, interfering in the normal development and function of organs and tissues in the body. Tyr is the precursor of catecholamines, secreted in response to stress by the adrenal medulla and paraganglia. The aim of this study was to evaluate plasma catecholamine and amino acid response to an escalating series of sympathetic stress tests in PKU patients. METHODS: Twelve males with classical PKU (aged 18-41 years) and ten healthy male controls were included in this study. The subjects were exposed to three different sympathetic stress stimulations: cold pressor, isometric handgrip, and peak treadmill tests to exhaustion. Physiological, metabolic, and hormonal changes were determined. RESULTS: Aerobic capacity (VO2max) was significantly lower in the PKU group (p = 0.018); however, relative VO2max was similar in the two groups during the spiroergometric test. No significant differences in norepinephrine or in epinephrine response were found between the two groups during the different stimulation tests. Blood Phe increased significantly in the PKU group compared with controls (p = 0.027) during the spiroergometric test, while Tyr levels remained stable in both groups. CONCLUSION: PKU itself might not influence stress-induced catecholamine changes. Only strenuous exercise increased blood Phe levels in PKU subjects.

Influence of exercise on thermographically determined surface temperatures of thoracic and pelvic limbs in horses.

OBJECTIVE: To determine the amount of time required for surface temperatures of thoracic and pelvic limbs in horses to return to pre-exercise temperatures after high-speed treadmill exercise, as detected via infrared thermographic imaging. DESIGN: Prospective study. ANIMALS: 6 Thoroughbreds. PROCEDURES: All horses had been trained on and conditioned to use of a high-speed treadmill. Baseline thermographic images were obtained 3 days prior to exercise (baseline). Horses were exercised on a treadmill at a walk for 5 minutes, a slow trot (3 m/s) for 5 minutes, a trot (5 to 6 m/s) for 5 minutes, and a slow gallop (6 to 8 m/s) for 5 minutes, then back to a trot for 3 minutes, a slow trot for 3 minutes, and a walk for 3 minutes prior to stopping. Thermal images were obtained immediately after stopping exercise (0 minutes) and 5, 15, 45, and 60 minutes and 6 hours after stopping exercise. Ambient temperature surrounding each horse was recorded. RESULTS: In all regions, significant differences in surface temperatures were detected between thermograms obtained before exercise and those obtained immediately after, 5 minutes after, and 15 minutes after exercise was stopped. There were no significant differences in surface temperatures between thermograms obtained before exercise and those obtained > or = 45 minutes after exercise was stopped. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, images generated via infrared thermography are not influenced by exercise-generated heat > or = 45 minutes after exercise is stopped.

Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model.

Heparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti-CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect. These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.

Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels.

BACKGROUND AND PURPOSE: Tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOalpha on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. MATERIAL AND METHODS: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOalpha at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOalpha on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1alpha expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOalpha and irradiation were also tested in vitro. RESULTS: In vitro, rHuEPOalpha treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOalpha administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1alpha expression but had no effect on tumor growth. At the same time rHuEPOalpha treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 +/- 4.7 mg and 34.9 +/- 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. CONCLUSION: rHuEPOalpha treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1alpha expression, but also by destroying tumoral vessels.

Conocimiento y medidas preventivas sobre neoplasia mamaria en usuarias de un centro de salud Ica, Perú 2010 / Knowledge and preventive measures on mammary neoplasia in women attending a health center Ica, Perú 2010

Objetivo: Determinar el conocimiento y medidas preventivas sobre neoplasia mamaria en usuarias de un centro de salud de Ica, 2010.Material y métodos: El estudio fue cuantitativo, de tipo descriptivo, y transversal, la muestra estuvo conformada por 80 usuarias que fueron seleccionadas a través del muestreo no probabilístico intencional, la técnica que se utilizó fue la encuesta. Resultados: En relación a los datos generales, el 40% tiene de 36 a 45 años de edad y tienen 2 hijos, el 64% tienen instrucción secundaria. Respecto al conocimiento que tienen sobre neoplasia mamaria, el 65% tienen nivel de conocimiento medio. El 66% realiza medidas preventivas desfavorables. Conclusiones: El nivel de conocimiento sobre neoplasia mamaria es medio, y las medidas preventivas son desfavorables, por lo que se recomienda el impulso de campañas educativas a la población de manera directa y a través de los medios de comunicación sobre el autoexamen de mama y patología mamaria, e intervenir en la detección temprana de cáncer de mama, capacitar al personal de salud tanto de atención primaria como secundaria, mediante programas de educación continua, para evaluar el cumplimiento de la promoción del autoexamen de mama, y elevar el grado de conocimiento de las usuarias sobre neoplasia mamaria. (AU)

Objective: To determine the knowledge and preventive measures on mammary neoplasia in women attending by a health center in Ica, 2010. Material and methods: The study was quantitative, descriptive, and transversal, the sample was composed of 80 users that were selected through the intentional non-probability sampling, the technique used was the survey. Results : In relation to the general information 40 % has from 36 to 45 years of age and they have 2 children, 64 % has secondary instruction. With regard to the knowledge that they have on neoplasia mammary, 65 % has level of average knowledge. 66 % realizes preventive unfavourable measures Conclusions:The level of knowledge on mammary neoplasia is average and the preventive measures are unfavourable. And should be recommended for the promotion of educational campaign to the population directly and through the media on the breast self-examination and breast pathology and take part in the early detection of breast cancer, train the staff of both of health care primary and secondary schools, through continuing education programs, to evaluate the compliance of the promotion of breast self-examination, and raising the degree of knowledge of the users on mammary neoplasia. (AU)